Conformational States of the Cytoprotective Protein Bcl-xL.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
06 10 2020
06 10 2020
Historique:
received:
25
03
2020
revised:
01
07
2020
accepted:
17
08
2020
pubmed:
6
9
2020
medline:
15
5
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
Bcl-xL is a major inhibitor of apoptosis, a fundamental homeostatic process of programmed cell death that is highly conserved across evolution. Because it plays prominent roles in cancer, Bcl-xL is a major target for anticancer therapy and for studies aimed at understanding its structure and activity. Although Bcl-xL is active primarily at intracellular membranes, most studies have focused on soluble forms of the protein lacking both the membrane-anchoring C-terminal tail and the intrinsically disordered loop, and this has resulted in a fragmented view of the protein's biological activity. Here, we describe the conformation of full-length Bcl-xL. Using NMR spectroscopy, molecular dynamics simulations, and isothermal titration calorimetry, we show how the three structural elements affect the protein's structure, dynamics, and ligand-binding activity in both its soluble and membrane-anchored states. The combined data provide information about the molecular basis for the protein's functionality and a view of its complex molecular mechanisms.
Identifiants
pubmed: 32888404
pii: S0006-3495(20)30642-1
doi: 10.1016/j.bpj.2020.08.014
pmc: PMC7567986
pii:
doi:
Substances chimiques
bcl-X Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1324-1334Subventions
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118186
Pays : United States
Informations de copyright
Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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