Article ; Online: SARAH Domain-Mediated MST2-RASSF Dimeric Interactions.
2016 Volume 12, Issue 10, Page(s) e1005051
Abstract: ... The regulation of MST1/2 includes both homo- and heterodimerization, mediated by helical SARAH domains ... RASSF5, and MST2 SARAH domains by using both atomistic molecular simulation techniques and experiments ... We construct and study models of MST2 homodimers and MST2-RASSF SARAH heterodimers, and we identify the factors ...
Abstract | RASSF enzymes act as key apoptosis activators and tumor suppressors, being downregulated in many human cancers, although their exact regulatory roles remain unknown. A key downstream event in the RASSF pathway is the regulation of MST kinases, which are main effectors of RASSF-induced apoptosis. The regulation of MST1/2 includes both homo- and heterodimerization, mediated by helical SARAH domains, though the underlying molecular interaction mechanism is unclear. Here, we study the interactions between RASSF1A, RASSF5, and MST2 SARAH domains by using both atomistic molecular simulation techniques and experiments. We construct and study models of MST2 homodimers and MST2-RASSF SARAH heterodimers, and we identify the factors that control their high molecular stability. In addition, we also analyze both computationally and experimentally the interactions of MST2 SARAH domains with a series of synthetic peptides particularly designed to bind to it, and hope that our approach can be used to address some of the challenging problems in designing new anti-cancer drugs. |
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MeSH term(s) | Binding Sites ; Carrier Proteins/chemistry ; Carrier Proteins/ultrastructure ; Cyclin-Dependent Kinase Inhibitor p15/chemistry ; Cyclin-Dependent Kinase Inhibitor p15/ultrastructure ; Dimerization ; Drosophila Proteins/chemistry ; Drosophila Proteins/ultrastructure ; Enzyme Activation ; Molecular Docking Simulation ; Protein Binding ; Protein Conformation ; Protein Domains |
Chemical Substances | CDKN2B protein, human ; Carrier Proteins ; Cyclin-Dependent Kinase Inhibitor p15 ; Drosophila Proteins ; RASSF protein, Drosophila |
Language | English |
Publishing date | 2016-10 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 2193340-6 |
ISSN | 1553-7358 ; 1553-734X |
ISSN (online) | 1553-7358 |
ISSN | 1553-734X |
DOI | 10.1371/journal.pcbi.1005051 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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