Dimerization model of the C-terminal RNA Recognition Motif of HuR
Human antigen R (HuR) is a ubiquitous 32kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3′ UnTranslated Regions (UTRs) of mRNAs. In addition to binding RNA molecules, the third domain (RRM3) is involved in HuR...
| Autores: | , , |
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| Tipo de documento: | artigo |
| Estado: | Versión enviada para evaluación y publicación |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Universidad de Sevilla (US) |
| Repositório: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/69174 |
| Acesso em linha: | https://hdl.handle.net/11441/69174 https://doi.org/10.1016/j.febslet.2015.03.013 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Dimerization Human antigen R (HuR) RNA Binding Protein RNA Recognition Motif (RRM) Brownian Dynamics (BD) Molecular Dynamics (MD) |
| Resumo: | Human antigen R (HuR) is a ubiquitous 32kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3′ UnTranslated Regions (UTRs) of mRNAs. In addition to binding RNA molecules, the third domain (RRM3) is involved in HuR oligomerization and apoptotic signaling. The RRM3 monomer is able to dimerize, with its self-binding affinity being dependent on ionic strength. Here we provide a deeper structural insight into the nature of the encounter complexes leading to the formation of RRM3 dimers by using Brownian Dynamics and Molecular Dynamics. Our computational data show that the initial unspecific encounter follows a downhill pathway until reaching an optimum conformation stabilized by hydrophobic interactions. |
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