Competing Roles of Ca2+ and Nonmuscle Myosin IIA on the Dynamics of the Metastasis-Associated Protein S100A4

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dc.authoridYildirim, Ahmet/0000-0003-1495-0288
dc.authoridTekpinar, Mustafa/0000-0002-0207-0446
dc.contributor.authorYildirim, Ahmet
dc.contributor.authorTekpinar, Mustafa
dc.contributor.authorWassenaar, Tsjerk A.
dc.date.accessioned2024-12-24T19:27:50Z
dc.date.available2024-12-24T19:27:50Z
dc.date.issued2021
dc.departmentSiirt Üniversitesi
dc.description.abstractThe calcium-binding protein S100A4 plays an important role in a wide range of biological processes such as cell motility, invasion, angiogenesis, survival, differentiation, contractility, and tumor metastasis and interacts with a range of partners. To understand the functional roles and interplay of S100A4 binding partners such as Ca2+ and nonmuscle myosin IIA (NMIIA), we used molecular dynamics simulations to investigate apo S100A4 and four holo S100A4 structures: S100A4 bound to Ca2+, S100A4 bound to NMIIA, S100A4 bound to Ca2+ and NMIIA, and a mutated S100A4 bound to Ca2+ and NMIIA. Our results show that two competing factors, namely, Ca2+-induced activation and NMIIA-induced inhibition, modulate the dynamics of S100A4 in a competitive manner. Moreover, Ca2+ binding results in enhanced dynamics, regulating the interactions of S100A4 with NMIIA, while NMIIA induces asymmetric dynamics between the chains of S100A4. The results also show that in the absence of Ca2+ the S100A4-NMIIA interaction is weak compared to that of between S100A4 bound to Ca2+ and NMIIA, which may offer a quick response to dropping calcium levels. In addition, certain mutations are shown to play a marked role on the dynamics of S100A4. The results described here contribute to understanding the interactions of S100A4 with NMIIA and the functional roles of Ca2+, NMIIA, and certain mutations on the dynamics of S100A4. The results of this study could be interesting for the development of inhibitors that exploit the shift of balance between the competing roles of Ca2+ and NMIIA.
dc.identifier.doi10.1021/acs.jpcb.1c02096
dc.identifier.endpage10071
dc.identifier.issn1520-6106
dc.identifier.issn1520-5207
dc.identifier.issue36
dc.identifier.pmid34464144
dc.identifier.scopus2-s2.0-85114869242
dc.identifier.scopusqualityQ2
dc.identifier.startpage10059
dc.identifier.urihttps://doi.org/10.1021/acs.jpcb.1c02096
dc.identifier.urihttps://hdl.handle.net/20.500.12604/6817
dc.identifier.volume125
dc.identifier.wosWOS:000697332700001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofJournal of Physical Chemistry B
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241222
dc.titleCompeting Roles of Ca2+ and Nonmuscle Myosin IIA on the Dynamics of the Metastasis-Associated Protein S100A4
dc.typeArticle

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