The high stability of the three-helix bundle UBA domain of p62 protein as revealed by molecular dynamics simulations

Autor(es)

Teixeira, Andre L. ^[1] ; Alves, Nelson A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Fis, FFCLRP, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Molecular Modeling; v. 27, n. 4 APR 2021.
• Citações Web of Science: 0

Resumo

The ubiquitin-associated (UBA) domain is an important motif in the modulation of many molecular functionalities. It has been mainly associated with ubiquitin-mediated proteolysis, a multistep mechanism in which undesirable proteins are tagged with polyubiquitin chains for degradation in the proteasome complex. Comparison among UBA domains reveals a quite small structural variability, displaying an overall fold with a tightly packed three-helix bundle, and a common conserved hydrophobic patch on their surface that is important for ubiquitin binding. Mutations in the UBA domain, mainly in the highly conserved hydrophobic patch, induce conformational instabilities, which can be related to weak affinity for ubiquitin. This raises the question whether such hydrophobic patch presents conserved structural arrangement for selective recognition and protein binding. A concern that led us to investigate the stability of the p62-UBA domain as a case study regarding its structural arrangement as a function of temperature and two NaCl concentrations. Our results reveal that the temperature range and ionic strengths considered in this work produced a negligible effect on the three-helix bundle fold of p62-UBA domain. (AU)

• Processo FAPESP: 16/04176-4 - Análise sistemática in silico do comportamento crítico do peptídeo amiloide beta e de alguns dos seus mutantes
• Beneficiário: Nelson Augusto Alves
• Modalidade de apoio: Auxílio à Pesquisa - Regular