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  1. Book ; Online: Function and Flexibility: Friend or Foe?

    Tompa, Peter / Pauwels, Kris

    2016  

    Abstract: Louis Sullivan (1856 - 1924) revolutionized architecture by designing the first skyscraper and he became famous by proclaiming that "form follows function". When x-ray crystallographers visualized the structures of proteins for the first time, the ... ...

    Abstract Louis Sullivan (1856 - 1924) revolutionized architecture by designing the first skyscraper and he became famous by proclaiming that "form follows function". When x-ray crystallographers visualized the structures of proteins for the first time, the structural biology field embraced the view that "function follows form" as the 3D-architecture of proteins could unveil various aspects of their function. Despite the original "1 gene - 1 protein structure - 1 function" relationship, nowadays a far more complicated picture emerges where the flexibility and dynamics of a protein can play a central role in a multitude of functions. The ultimate form(s) that a protein adopt when interacting with (a) partner molecule(s) are the most biologically relevant and in this context Sullivan's quote is still appropriate: the conformation that the protein adopts follows from the function of that protein.-

    Despite the fact that many well-characterized proteins have a well-folded structure, there is a growing interest in the conformational flexibility within proteins. This flexibility is also a balanced phenomenon: excess of flexibility can be detrimental for protein behaviour, as well as the lack thereof. Notwithstanding its importance, studying intrinsically disordered protein regions or conformational rearrangements can be a very challenging. Therefore, flexibility can be perceived as a friend or a foe, depending on the context. This e-book showcases the impact of the study of protein flexibility on the structural biology field and presents protein flexibility in the context of disease as well as its benign aspects. As detailed knowledge of the structural aspects of polypeptides remains essential to comprehend protein function, one of the future challenges for structural biology also lies with large macromolecular protein complexes.-

    Also there the dynamics and flexibility are essential for proper functioning and molecular movement, which is an important aspect of living matter. This challenge stimulated the development of advanced techniques to study protein flexibility and the use of those techniques to address fundamental biological and biomedical problems. Those innovations should help us to unravel the intimate link between protein function and flexibility and explore new horizons
    Keywords Science (General)
    Size 1 electronic resource (102 p.)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT020090691
    ISBN 9782889199723 ; 288919972X
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Book: Structure and function of intrinscially [intrinsically] disordered proteins

    Tompa, Peter

    2010  

    Author's details Peter Tompa
    Keywords Protein Conformation ; Protein Denaturation ; Protein Folding ; Structure-Activity Relationship ; Proteins/Pathophysiology ; Proteins/Structure-activity relationships ; Proteins/Metabolism/Disorders ; Proteins/Conformation ; Proteins/Denaturation ; Protein folding
    Subject code 612.398
    Language English
    Size XXVII, 331 S. : Ill., graph. Darst.
    Publisher CRC Press
    Publishing place Boca Raton u.a.
    Publishing country United States
    Document type Book
    Note Includes bibliographical references and index
    HBZ-ID HT016058983
    ISBN 978-1-4200-7892-3 ; 1-4200-7892-5
    Database Catalogue ZB MED Medicine, Health

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  3. Book: Fuzziness

    Fuxreiter, Monika / Tompa, Peter

    structural disorder in protein complexes

    (Advances in experimental medicine and biology ; 725)

    2012  

    Author's details ed. by Monika Fuxreiter; Peter Tompa
    Series title Advances in experimental medicine and biology ; 725
    Collection
    Keywords Protein Conformation ; Protein Denaturation
    Language English
    Size XX, 194 S. : Ill., graph. Darst.
    Publisher Springer
    Publishing place New York
    Publishing country United States
    Document type Book
    Note Includes bibliographical references and index ; Fuzzy complexes : a more stochastic view of protein function / Monika Fuxreiter and Peter Tompa -- Dynamic fuzziness during linker histone action / Steven J. McBryant and Jeffrey C. Hansen -- Intrinsic protein flexibility in regulation of cell proliferation : advantages for signaling and opportunities for novel therapeutics / Ariele Viacava Follis, Charles A. Galea, and Richard W. Kriwacki -- Interplay between protein order, disorder and oligomericity in receptor signaling / Alexander B. Sigalov -- Consequences of fuzziness in the NFB/IB interaction / Elizabeth A. Komives -- Roles for intrinsic disorder and ̂fuzziness in generating context specific function in ultrabithorax : a hox transcription factor / Sarah E. Bondos and Hao Ching Hsiao -- Molecular recognition by the EWS transcriptional activation domain / Kevin A.W. Lee -- The measles virus NTAILXD complex : an illustrative example of fuzziness / Sonia Longhi -- Fuzziness in the core of the human pathogenic viruses HCV and HIV / Roland Ivanyi Nagy and Jean Luc Darlix -- Structural disorder and protein elasticity / Sarah Rauscher and Røgis Pomès
    HBZ-ID HT017115856
    ISBN 978-1-4614-0658-7 ; 1-4614-0658-7
    Database Catalogue ZB MED Medicine, Health

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  4. Article: First Records of Possibly Human Pathogenic

    Tompa, Eszter / Jaenson, Thomas G T / Wilhelmsson, Peter

    Microorganisms

    2023  Volume 11, Issue 2

    Abstract: The Soprano pipistrelle bat, ...

    Abstract The Soprano pipistrelle bat,
    Language English
    Publishing date 2023-01-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms11020357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Reply to "Intrinsic protein disorder uncouples affinity from binding specificity".

    Lázár, Tamás / Tantos, Agnes / Tompa, Peter / Schad, Eva

    Protein science : a publication of the Protein Society

    2023  Volume 32, Issue 4, Page(s) e4601

    MeSH term(s) Proteins ; Binding Sites
    Chemical Substances Proteins
    Language English
    Publishing date 2023-02-18
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1106283-6
    ISSN 1469-896X ; 0961-8368
    ISSN (online) 1469-896X
    ISSN 0961-8368
    DOI 10.1002/pro.4601
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Glioblastoma epigenomics discloses a complex biology and potential therapeutic targets.

    Krabóth, Zoltán / Tompa, Márton / Urbán, Péter / Gálik, Bence / Kajtár, Béla / Gyenesei, Attila / Kálmán, Bernadette

    Ideggyogyaszati szemle

    2024  Volume 77, Issue 1-2, Page(s) 27–37

    Abstract: Background and purpose: ... Glioblastoma (GBM), a highly aggressive form of brain tumors, has been extensively studied using OMICS methods, and the most characteristic molecular determinants have been incorporated into the histopathological diagnosis. ... ...

    Title translation A glioblastoma-epigenomika komplex biológiai folyamatokat és potenciális terápiás célpontokat tár fel.
    Abstract Background and purpose:

    Glioblastoma (GBM), a highly aggressive form of brain tumors, has been extensively studied using OMICS methods, and the most characteristic molecular determinants have been incorporated into the histopathological diagnosis. Research data, nevertheless, only partially have been adopted in clinical practice. Here we aimed to present results of our epige­no­mic GBM profiling to better understand early and late determinants of these tumors, and to share main elements of our findings with practicing professionals.

    .
    Methods:

    GBM specimens were surgically obtained after first diagnosis (GBM1) and at recurrence (GBM2). DNA was extracted from 24 sequential pairs of formalin-fixed, paraffin-embedded tumor tissues. The Reduced Representation Bisulfite Sequencing kit was used for library preparation. Pooled libraries were sequenced on an Illumina NextSeq 550 instrument. Methylation controls (MC) were obtained from a publicly available database. Bioinformatic analyses were performed to identify differentially methylated pathways and their elements in cohorts of MC, GBM1 and GBM2.

    .
    Results:

    Several differentially methylated pathways involved in basic intracellular and brain tissue developmental processes were identified in the GBM1 vs. MC and GBM2 vs. MC comparisons. Among differentially me­thylated pathways, those involved in immune regulation, neurotransmitter (particularly dopaminergic, noradrenergic and glutaminergic) responses and regulation of stem cell differentiation and proliferation stood out in the GBM2 vs. GBM1 comparisons.

    .
    Conclusion:

    Our study revealed biological complexity of early and late gliomagenesis encompassing mechanisms from basic intracellular through distorted neurodevelopmental processes to more specific immune and highjacked neurotransmitter pathways in the tumor microenvironment. These findings may offer considerations for therapeutic approaches.

    .
    MeSH term(s) Humans ; Glioblastoma/pathology ; Epigenomics ; DNA Methylation ; Brain/pathology ; Brain Neoplasms/pathology ; Neurotransmitter Agents ; Gene Expression Regulation, Neoplastic ; Tumor Microenvironment
    Chemical Substances Neurotransmitter Agents
    Language English
    Publishing date 2024-02-06
    Publishing country Hungary
    Document type Journal Article
    ZDB-ID 2240317-6
    ISSN 0019-1442
    ISSN 0019-1442
    DOI 10.18071/isz.77.0027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The principle of conformational signaling.

    Tompa, Peter

    Chemical Society reviews

    2016  Volume 45, Issue 15, Page(s) 4252–4284

    Abstract: Signal transduction is the primary process by which cells respond to changes in their physical and chemical environments. Cellular response is initiated through a signaling protein (a receptor), which interacts with the "signal", most often a novel ... ...

    Abstract Signal transduction is the primary process by which cells respond to changes in their physical and chemical environments. Cellular response is initiated through a signaling protein (a receptor), which interacts with the "signal", most often a novel molecule outside or inside the cell. The mechanism of activation of the receptor is a conformational change and/or covalent modification, which then sets in motion a signaling pathway, i.e. a cascade of modification and binding events that relay and amplify the message to eventually alter the state of the cell. In reflection of this general perception, concepts such as the "second messenger" and the "phosphorylation cascade" dominate our views of signal transduction. The idea I advocate here is that the non-covalent change in protein conformation itself might serve as the initial or intermittent "signal" in the cascade, and it is often the primary event being recognized and interpreted by downstream receptor(s). This signaling principle is intertwined with many other cellular regulatory concepts, such as (pathway) allostery, conformational spread, induced folding/unfolding, conformational memory, the hierarchical assembly of complexes, and the action of regulatory chaperones and prions. By elaborating on many examples and also recent advances in experimental methodology, I show that conformational signaling, although thus far underappreciated, is a general and robust signaling principle that most of the time operates in close interplay with covalent signals in the cell.
    Language English
    Publishing date 2016-07-25
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1472875-8
    ISSN 1460-4744 ; 0306-0012
    ISSN (online) 1460-4744
    ISSN 0306-0012
    DOI 10.1039/c6cs00011h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Intrinsic protein disorder uncouples affinity from binding specificity.

    Lazar, Tamas / Tantos, Agnes / Tompa, Peter / Schad, Eva

    Protein science : a publication of the Protein Society

    2022  Volume 31, Issue 11, Page(s) e4455

    Abstract: Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins often function by molecular recognition, in which they undergo induced folding. Based on prior generalizations, the idea prevails in the IDP field that due ... ...

    Abstract Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins often function by molecular recognition, in which they undergo induced folding. Based on prior generalizations, the idea prevails in the IDP field that due to the entropic penalty of induced folding, the major functional advantage associated with this binding mode is "uncoupling" specificity from binding strength. Nevertheless, both weaker binding and high specificity of IDPs/IDRs rest on limited experimental observations, making these assumptions more speculations than evidence-supported facts. The issue is also complicated by the rather vague concept of specificity that lacks an exact measure, such as the K
    MeSH term(s) Intrinsically Disordered Proteins/chemistry ; Protein Binding ; Protein Conformation ; Protein Folding
    Chemical Substances Intrinsically Disordered Proteins
    Language English
    Publishing date 2022-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1106283-6
    ISSN 1469-896X ; 0961-8368
    ISSN (online) 1469-896X
    ISSN 0961-8368
    DOI 10.1002/pro.4455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Multisteric regulation by structural disorder in modular signaling proteins: an extension of the concept of allostery.

    Tompa, Peter

    Chemical reviews

    2014  Volume 114, Issue 13, Page(s) 6715–6732

    MeSH term(s) Allosteric Regulation ; Humans ; Intrinsically Disordered Proteins/chemistry ; Intrinsically Disordered Proteins/physiology ; Models, Biological ; Protein Conformation ; Signal Transduction/physiology
    Chemical Substances Intrinsically Disordered Proteins
    Language English
    Publishing date 2014-07-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 207949-5
    ISSN 1520-6890 ; 0009-2665
    ISSN (online) 1520-6890
    ISSN 0009-2665
    DOI 10.1021/cr4005082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The role of ordered cooperative assembly in biomolecular condensates.

    Korkmazhan, Elgin / Tompa, Peter / Dunn, Alexander R

    Nature reviews. Molecular cell biology

    2021  Volume 22, Issue 10, Page(s) 647–648

    MeSH term(s) Animals ; Humans ; Multiprotein Complexes/chemistry ; Multiprotein Complexes/metabolism ; Organelles/chemistry ; Organelles/metabolism ; Phase Transition ; Proteins/chemistry ; Proteins/metabolism ; Signal Transduction/physiology
    Chemical Substances Multiprotein Complexes ; Proteins
    Language English
    Publishing date 2021-08-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-021-00408-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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