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Article: Reconstitution of Functionalized Transmembrane Domains of Receptor Proteins into Biomimetic Membranes

Scott, Daniel R / Silin Vitalii / Nanda Hirsh

Langmuir. 2015 Aug. 25, v. 31, no. 33

2015

Abstract: For integral membrane proteins, an assessment of their structures and interactions within a biomimetic lipid bilayer environment is critical for evaluating their cellular function. Hydrophobic sequences prevalent within transmembrane domains, however, ... ...

Abstract	For integral membrane proteins, an assessment of their structures and interactions within a biomimetic lipid bilayer environment is critical for evaluating their cellular function. Hydrophobic sequences prevalent within transmembrane domains, however, make these proteins susceptible to aggregation and, thus, create difficulties in examining their structural and functional properties via canonical techniques. Working exclusively with single-pass transmembrane (TM) segments of bitopic membrane proteins, in the form of soluble peptides, bypasses many of the pitfalls of full-length protein preparations while allowing for the opportunity to examine the properties of TM domains within biomimetic membrane environments. In this study, peptides mimicking the TM domains of the epidermal growth factor receptor (EGFR) and CD4 co-receptor, both cell-signaling surface receptors, have been reconstituted into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers. The formation of their native Î±-helical structures within vesicle membranes was observed from circular dichroism, and full partition of the peptides into the membrane was demonstrated by tryptophan fluorescence and neutron reflectivity (NR). Using an engineered planar lipid bilayer system ideal for surface characterization methods, such as surface plasmon resonance (SPR) and NR, the TM peptides, functionalized with a N-terminal biotin tag, proved capable of âactivatingâ a membrane surface, as evidenced by the capture of streptavidin. On the basis of these initial assessments, we anticipate these membrane-bound peptides will provide a versatile platform for understanding the intricate roles of receptor TM domains in cell signaling.
Keywords	biomimetics ; biotin ; circular dichroism spectroscopy ; epidermal growth factor receptors ; fluorescence ; functional properties ; hydrophobicity ; lipid bilayers ; neutrons ; peptides ; streptavidin ; surface plasmon resonance ; tryptophan
Language	English
Dates of publication	2015-0825
Size	p. 9115-9124.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021%2Facs.langmuir.5b01990
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Reconstitution of Functionalized Transmembrane Domains of Receptor Proteins into Biomimetic Membranes.

Scott, Daniel R / Silin, Vitalii / Nanda, Hirsh

Langmuir : the ACS journal of surfaces and colloids

2015 Volume 31, Issue 33, Page(s) 9115–9124

Abstract	For integral membrane proteins, an assessment of their structures and interactions within a biomimetic lipid bilayer environment is critical for evaluating their cellular function. Hydrophobic sequences prevalent within transmembrane domains, however, make these proteins susceptible to aggregation and, thus, create difficulties in examining their structural and functional properties via canonical techniques. Working exclusively with single-pass transmembrane (TM) segments of bitopic membrane proteins, in the form of soluble peptides, bypasses many of the pitfalls of full-length protein preparations while allowing for the opportunity to examine the properties of TM domains within biomimetic membrane environments. In this study, peptides mimicking the TM domains of the epidermal growth factor receptor (EGFR) and CD4 co-receptor, both cell-signaling surface receptors, have been reconstituted into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers. The formation of their native α-helical structures within vesicle membranes was observed from circular dichroism, and full partition of the peptides into the membrane was demonstrated by tryptophan fluorescence and neutron reflectivity (NR). Using an engineered planar lipid bilayer system ideal for surface characterization methods, such as surface plasmon resonance (SPR) and NR, the TM peptides, functionalized with a N-terminal biotin tag, proved capable of "activating" a membrane surface, as evidenced by the capture of streptavidin. On the basis of these initial assessments, we anticipate these membrane-bound peptides will provide a versatile platform for understanding the intricate roles of receptor TM domains in cell signaling.
MeSH term(s)	CD4 Antigens/chemistry ; Humans ; Lipid Bilayers/chemistry ; Phosphatidylcholines/chemistry ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/chemistry
Chemical Substances	CD4 Antigens ; Lipid Bilayers ; Phosphatidylcholines ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; 1-palmitoyl-2-oleoylphosphatidylcholine (TE895536Y5)
Language	English
Publishing date	2015-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.5b01990
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Article ; Online: Structural Characterization and Modeling of a Respiratory Syncytial Virus Fusion Glycoprotein Nanoparticle Vaccine in Solution.

Krueger, Susan / Curtis, Joseph E / Scott, Daniel R / Grishaev, Alexander / Glenn, Greg / Smith, Gale / Ellingsworth, Larry / Borisov, Oleg / Maynard, Ernest L

Molecular pharmaceutics

2020 Volume 18, Issue 1, Page(s) 359–376

Abstract: The respiratory syncytial virus (RSV) fusion (F) protein/polysorbate 80 (PS80) nanoparticle vaccine is the most clinically advanced vaccine for maternal immunization and protection of newborns against RSV infection. It is composed of a near-full-length ... ...

Abstract	The respiratory syncytial virus (RSV) fusion (F) protein/polysorbate 80 (PS80) nanoparticle vaccine is the most clinically advanced vaccine for maternal immunization and protection of newborns against RSV infection. It is composed of a near-full-length RSV F glycoprotein, with an intact membrane domain, formulated into a stable nanoparticle with PS80 detergent. To understand the structural basis for the efficacy of the vaccine, a comprehensive study of its structure and hydrodynamic properties in solution was performed. Small-angle neutron scattering experiments indicate that the nanoparticle contains an average of 350 PS80 molecules, which form a cylindrical micellar core structure and five RSV F trimers that are arranged around the long axis of the PS80 core. All-atom models of full-length RSV F trimers were built from crystal structures of the soluble ectodomain and arranged around the long axis of the PS80 core, allowing for the generation of an ensemble of conformations that agree with small-angle neutron and X-ray scattering data as well as transmission electron microscopy (TEM) images. Furthermore, the hydrodynamic size of the RSV F nanoparticle was found to be modulated by the molar ratio of PS80 to protein, suggesting a mechanism for nanoparticle assembly involving addition of RSV F trimers to and growth along the long axis of the PS80 core. This study provides structural details of antigen presentation and conformation in the RSV F nanoparticle vaccine, helping to explain the induction of broad immunity and observed clinical efficacy. Small-angle scattering methods provide a general strategy to visualize surface glycoproteins from other pathogens and to structurally characterize nanoparticle vaccines.
MeSH term(s)	Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/immunology ; Glycoproteins/chemistry ; Glycoproteins/immunology ; Nanoparticles/chemistry ; Respiratory Syncytial Virus Infections/immunology ; Respiratory Syncytial Virus Vaccines/chemistry ; Respiratory Syncytial Virus Vaccines/immunology ; Respiratory Syncytial Virus, Human/chemistry ; Respiratory Syncytial Virus, Human/immunology ; Vaccination/methods
Chemical Substances	Antibodies, Neutralizing ; Glycoproteins ; Respiratory Syncytial Virus Vaccines
Language	English
Publishing date	2020-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.0c00986
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Article ; Online: Differential utilization of binding loop flexibility in T cell receptor ligand selection and cross-reactivity.

Ayres, Cory M / Scott, Daniel R / Corcelli, Steven A / Baker, Brian M

Scientific reports

2016 Volume 6, Page(s) 25070

Abstract: Complementarity determining region (CDR) loop flexibility has been suggested to play an important role in the selection and binding of ligands by T cell receptors (TCRs) of the cellular immune system. However, questions remain regarding the role of loop ... ...

Abstract	Complementarity determining region (CDR) loop flexibility has been suggested to play an important role in the selection and binding of ligands by T cell receptors (TCRs) of the cellular immune system. However, questions remain regarding the role of loop motion in TCR binding, and crystallographic structures have raised questions about the extent to which generalizations can be made. Here we studied the flexibility of two structurally well characterized αβ TCRs, A6 and DMF5. We found that the two receptors utilize loop motion very differently in ligand binding and cross-reactivity. While the loops of A6 move rapidly in an uncorrelated fashion, those of DMF5 are substantially less mobile. Accordingly, the mechanisms of binding and cross-reactivity are very different between the two TCRs: whereas A6 relies on conformational selection to select and bind different ligands, DMF5 uses a more rigid, permissive architecture with greater reliance on slower motions or induced-fit. In addition to binding site flexibility, we also explored whether ligand-binding resulted in common dynamical changes in A6 and DMF5 that could contribute to TCR triggering. Although binding-linked motional changes propagated throughout both receptors, no common features were observed, suggesting that changes in nanosecond-level TCR structural dynamics do not contribute to T cell signaling.
Language	English
Publishing date	2016--27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep25070
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Article ; Online: The basis for limited specificity and MHC restriction in a T cell receptor interface.

Piepenbrink, Kurt H / Blevins, Sydney J / Scott, Daniel R / Baker, Brian M

Nature communications

2013 Volume 4, Page(s) 1948

Abstract: αβ T cell receptors (TCRs) recognize peptides presented by major histocompatibility complex (MHC) proteins using multiple complementarity-determining region (CDR) loops. TCRs display an array of poorly understood recognition properties, including ... ...

Abstract	αβ T cell receptors (TCRs) recognize peptides presented by major histocompatibility complex (MHC) proteins using multiple complementarity-determining region (CDR) loops. TCRs display an array of poorly understood recognition properties, including specificity, crossreactivity and MHC restriction. Here we report a comprehensive thermodynamic deconstruction of the interaction between the A6 TCR and the Tax peptide presented by the class I MHC HLA-A*0201, uncovering the physical basis for the receptor's recognition properties. Broadly, our findings are in conflict with widely held generalities regarding TCR recognition, such as the relative contributions of central and peripheral peptide residues and the roles of the hypervariable and germline CDR loops in engaging peptide and MHC. Instead, we find that the recognition properties of the receptor emerge from the need to engage the composite peptide/MHC surface, with the receptor utilizing its CDR loops in a cooperative fashion such that specificity, crossreactivity and MHC restriction are inextricably linked.
MeSH term(s)	Complementarity Determining Regions/immunology ; Complementarity Determining Regions/metabolism ; Conserved Sequence ; Gene Products, tax/chemistry ; Gene Products, tax/immunology ; Gene Products, tax/metabolism ; HLA-A2 Antigen/chemistry ; HLA-A2 Antigen/genetics ; HLA-A2 Antigen/immunology ; HLA-A2 Antigen/metabolism ; Humans ; Major Histocompatibility Complex/immunology ; Models, Molecular ; Mutant Proteins/chemistry ; Mutant Proteins/metabolism ; Mutation/genetics ; Peptides/chemistry ; Peptides/immunology ; Peptides/metabolism ; Protein Binding ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism
Chemical Substances	Complementarity Determining Regions ; Gene Products, tax ; HLA-A2 Antigen ; Mutant Proteins ; Peptides ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2013-06-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms2948
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Article ; Online: Structural and dynamic control of T-cell receptor specificity, cross-reactivity, and binding mechanism.

Baker, Brian M / Scott, Daniel R / Blevins, Sydney J / Hawse, William F

Immunological reviews

2012 Volume 250, Issue 1, Page(s) 10–31

Abstract: Over the past two decades, structural biology has shown how T-cell receptors engage peptide/major histocompatibility complex (MHC) complexes and provided insight into the mechanisms underlying antigen specificity and cross-reactivity. Here we review and ... ...

Abstract	Over the past two decades, structural biology has shown how T-cell receptors engage peptide/major histocompatibility complex (MHC) complexes and provided insight into the mechanisms underlying antigen specificity and cross-reactivity. Here we review and contextualize our contributions, which have emphasized the influence of structural changes and molecular flexibility. A repeated observation is the presence of conformational melding, in which the T-cell receptor (TCR), peptide, and in some cases, MHC protein cooperatively adjust in order for recognition to proceed. The structural changes reflect the intrinsic dynamics of the unligated proteins. Characterization of the dynamics of unligated TCR shows how binding loop motion can influence TCR cross-reactivity as well as specificity towards peptide and MHC. Examination of peptide dynamics indicates not only peptide-specific variation but also a peptide dependence to MHC flexibility. This latter point emphasizes that the TCR engages a composite peptide/MHC surface and that physically the receptor makes little distinction between the peptide and MHC. Much additional evidence for this can be found within the database of available structures, including our observations of a peptide dependence to the TCR binding mode and structural compensations for altered interatomic interactions, in which lost TCR-peptide interactions are replaced with TCR-MHC interactions. The lack of a hard-coded physical distinction between peptide and MHC has implications not only for specificity and cross-reactivity but also the mechanisms underlying MHC restriction as well as attempts to modulate and control TCR recognition.
MeSH term(s)	Animals ; Antigens/chemistry ; Antigens/immunology ; Antigens/metabolism ; Binding Sites ; Cross Reactions ; Humans ; Lymphocyte Activation ; Major Histocompatibility Complex/immunology ; Mice ; Models, Molecular ; Peptides/chemistry ; Peptides/immunology ; Peptides/metabolism ; Protein Binding ; Protein Conformation ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Cell Antigen Receptor Specificity ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Antigens ; Peptides ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2012-10-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/j.1600-065X.2012.01165.x
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Article ; Online: Limitations of time-resolved fluorescence suggested by molecular simulations: assessing the dynamics of T cell receptor binding loops.

Scott, Daniel R / Vardeman, Charles F / Corcelli, Steven A / Baker, Brian M

Biophysical journal

2012 Volume 103, Issue 12, Page(s) 2532–2540

Abstract: Time-resolved fluorescence anisotropy (TRFA) has a rich history in evaluating protein dynamics. Yet as often employed, TRFA assumes that the motional properties of a covalently tethered fluorescent probe accurately portray the motional properties of the ... ...

Abstract	Time-resolved fluorescence anisotropy (TRFA) has a rich history in evaluating protein dynamics. Yet as often employed, TRFA assumes that the motional properties of a covalently tethered fluorescent probe accurately portray the motional properties of the protein backbone at the probe attachment site. In an extensive survey using TRFA to study the dynamics of the binding loops of a αβ T cell receptor, we observed multiple discrepancies between the TRFA data and previously published results that led us to question this assumption. We thus simulated several of the experimentally probed systems using a protocol that permitted accurate determination of probe and protein time correlation functions. We found excellent agreement in the decays of the experimental and simulated correlation functions. However, the motional properties of the probe were poorly correlated with those of the backbone of both the labeled and unlabeled protein. Our results warrant caution in the interpretation of TRFA data and suggest further studies to ascertain the extent to which probe dynamics reflect those of the protein backbone. Meanwhile, the agreement between experiment and computation validates the use of molecular dynamics simulations as an accurate tool for exploring the molecular motion of T cell receptors and their binding loops.
MeSH term(s)	Amino Acid Sequence ; Complementarity Determining Regions/chemistry ; Complementarity Determining Regions/metabolism ; Fluorescence Polarization ; Molecular Dynamics Simulation ; Protein Binding ; Protein Structure, Tertiary ; Time Factors
Chemical Substances	Complementarity Determining Regions
Language	English
Publishing date	2012-12-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2012.10.037
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Article: Limitations of Time-Resolved Fluorescence Suggested by Molecular Simulations: Assessing the Dynamics of T cell Receptor Binding Loops

Scott, Daniel R / Vardeman, Charles F., II / Corcelli, Steven A / Baker, Brian M

Biophysical journal. 2012 Dec. 19, v. 103, no. 12

2012

Abstract	Time-resolved fluorescence anisotropy (TRFA) has a rich history in evaluating protein dynamics. Yet as often employed, TRFA assumes that the motional properties of a covalently tethered fluorescent probe accurately portray the motional properties of the protein backbone at the probe attachment site. In an extensive survey using TRFA to study the dynamics of the binding loops of a αβ T cell receptor, we observed multiple discrepancies between the TRFA data and previously published results that led us to question this assumption. We thus simulated several of the experimentally probed systems using a protocol that permitted accurate determination of probe and protein time correlation functions. We found excellent agreement in the decays of the experimental and simulated correlation functions. However, the motional properties of the probe were poorly correlated with those of the backbone of both the labeled and unlabeled protein. Our results warrant caution in the interpretation of TRFA data and suggest further studies to ascertain the extent to which probe dynamics reflect those of the protein backbone. Meanwhile, the agreement between experiment and computation validates the use of molecular dynamics simulations as an accurate tool for exploring the molecular motion of T cell receptors and their binding loops.
Keywords	T-lymphocytes ; fluorescence ; molecular dynamics ; receptors ; surveys
Language	English
Dates of publication	2012-1219
Size	p. 2532-2540.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2012.10.037
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Article ; Online: Freezing/Thawing without Cryoprotectant Damages Native but not Decellularized Porcine Renal Tissue.

Poornejad, Nafiseh / Frost, Timothy S / Scott, Daniel R / Elton, Brinden B / Reynolds, Paul R / Roeder, Beverly L / Cook, Alonzo D

Organogenesis

2015 Volume 11, Issue 1, Page(s) 30–45

Abstract: Whole organ decellularization of porcine renal tissue and recellularization with a patient's own cells would potentially overcome immunorejection, which is one of the most significant problems with allogeneic kidney transplantation. However, there are ... ...

Abstract	Whole organ decellularization of porcine renal tissue and recellularization with a patient's own cells would potentially overcome immunorejection, which is one of the most significant problems with allogeneic kidney transplantation. However, there are obstacles to achieving this goal, including preservation of the decellularized extracellular matrix (ECM), identifying the proper cell types, and repopulating the ECM before transplantation. Freezing biological tissue is the best option to avoid spoilage; however, it may damage the structure of the tissue or disrupt cellular membranes through ice crystal formation. Cryoprotectants have been used to repress ice formation during freezing, although cell toxicity can still occur. The effect of freezing/thawing on native (n = 10) and decellularized (n = 10) whole porcine kidneys was studied without using cryoprotectants. Results showed that the elastic modulus of native kidneys was reduced by a factor of 22 (P < 0.0001) by freezing/thawing or decellularization, while the elastic modulus for decellularized ECM was essentially unchanged by the freezing/thawing process (p = 0.0636). Arterial pressure, representative of structural integrity, was also reduced by a factor of 52 (P < 0.0001) after freezing/thawing for native kidneys, compared to a factor of 43 (P < 0.0001) for decellularization and a factor of 4 (P < 0.0001) for freezing/thawing decellularized structures. Both freezing/thawing and decellularization reduced stiffness, but the reductions were not additive. Investigation of the microstructure of frozen/thawed native and decellularized renal tissues showed increased porosity due to cell removal and ice crystal formation. Orcein and Sirius staining showed partial damage to elastic and collagen fibers after freezing/thawing. It was concluded that cellular damage and removal was more responsible for reducing stiffness than fibril destruction. Cell viability and growth were demonstrated on decellularized frozen/thawed and non-frozen samples using human renal cortical tubular epithelial (RCTE) cells over 12 d. No adverse effect on the ability to recellularize after freezing/thawing was observed. It is recommended that porcine kidneys be frozen prior to decellularization to prevent contamination, and after decellularization to prevent protein denaturation. Cryoprotectants may still be necessary, however, during storage and transportation after recellularization.
MeSH term(s)	Animals ; Arterial Pressure ; Biomechanical Phenomena ; Cell Line ; Compressive Strength ; Cryoprotective Agents/chemistry ; Elastic Modulus ; Extracellular Matrix/metabolism ; Freezing ; Humans ; Kidney/blood supply ; Kidney/ultrastructure ; Microscopy, Electron, Scanning ; Swine ; Tissue Scaffolds/chemistry
Chemical Substances	Cryoprotective Agents
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1555-8592
ISSN (online)	1555-8592
DOI	10.1080/15476278.2015.1022009
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Article ; Online: Disparate degrees of hypervariable loop flexibility control T-cell receptor cross-reactivity, specificity, and binding mechanism.

Scott, Daniel R / Borbulevych, Oleg Y / Piepenbrink, Kurt H / Corcelli, Steven A / Baker, Brian M

Journal of molecular biology

2011 Volume 414, Issue 3, Page(s) 385–400

Abstract: αβ T-cell receptors (TCRs) recognize multiple antigenic peptides bound and presented by major histocompatibility complex molecules. TCR cross-reactivity has been attributed in part to the flexibility of TCR complementarity-determining region (CDR) loops, ...

Abstract	αβ T-cell receptors (TCRs) recognize multiple antigenic peptides bound and presented by major histocompatibility complex molecules. TCR cross-reactivity has been attributed in part to the flexibility of TCR complementarity-determining region (CDR) loops, yet there have been limited direct studies of loop dynamics to determine the extent of its role. Here we studied the flexibility of the binding loops of the αβ TCR A6 using crystallographic, spectroscopic, and computational methods. A significant role for flexibility in binding and cross-reactivity was indicated only for the CDR3α and CDR3β hypervariable loops. Examination of the energy landscapes of these two loops indicated that CDR3β possesses a broad, smooth energy landscape, leading to rapid sampling in the free TCR of a range of conformations compatible with different ligands. The landscape for CDR3α is more rugged, resulting in more limited conformational sampling that leads to specificity for a reduced set of peptides as well as the major histocompatibility complex protein. In addition to informing on the mechanisms of cross-reactivity and specificity, the energy landscapes of the two loops indicate a complex mechanism for TCR binding, incorporating elements of both conformational selection and induced fit in a manner that blends features of popular models for TCR recognition.
MeSH term(s)	Anisotropy ; Calorimetry/methods ; Complementarity Determining Regions/chemistry ; Computer Simulation ; Dimerization ; HLA-A2 Antigen/chemistry ; Humans ; Immune System ; Ligands ; Major Histocompatibility Complex ; Molecular Conformation ; Peptides/chemistry ; Protein Binding ; Protein Conformation ; Receptors, Antigen, T-Cell/chemistry
Chemical Substances	Complementarity Determining Regions ; HLA-A2 Antigen ; Ligands ; Peptides ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2011-10-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2011.10.006
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