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The Structural Biology of Bcl-x(L)

Interactions between the pro-survival and pro-apoptotic members of the Bcl-2 family of proteins dictate whether a cell lives or dies. Much of our knowledge of the molecular details of these interactions has come from biochemical and structural studies on the pro-survival protein Bcl-x(L). The first...

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Autores principales: Lee, Erinna F., Fairlie, W. Douglas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540150/
https://www.ncbi.nlm.nih.gov/pubmed/31067648
http://dx.doi.org/10.3390/ijms20092234
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author Lee, Erinna F.
Fairlie, W. Douglas
author_facet Lee, Erinna F.
Fairlie, W. Douglas
author_sort Lee, Erinna F.
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description Interactions between the pro-survival and pro-apoptotic members of the Bcl-2 family of proteins dictate whether a cell lives or dies. Much of our knowledge of the molecular details of these interactions has come from biochemical and structural studies on the pro-survival protein Bcl-x(L). The first high-resolution structure of any Bcl-2 family member was of Bcl-x(L), which revealed the conserved topology amongst all family members. Subsequent structures of Bcl-x(L) complexes with pro-apoptotic ligands demonstrated the general features of all pro-survival:pro-apoptotic complexes. Structural studies involving Bcl-x(L) were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic. This article will review our current knowledge of the structural biology of Bcl-x(L) and how this has impacted our understanding of the molecular details of the intrinsic apoptotic pathway.
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spelling pubmed-65401502019-06-04 The Structural Biology of Bcl-x(L) Lee, Erinna F. Fairlie, W. Douglas Int J Mol Sci Review Interactions between the pro-survival and pro-apoptotic members of the Bcl-2 family of proteins dictate whether a cell lives or dies. Much of our knowledge of the molecular details of these interactions has come from biochemical and structural studies on the pro-survival protein Bcl-x(L). The first high-resolution structure of any Bcl-2 family member was of Bcl-x(L), which revealed the conserved topology amongst all family members. Subsequent structures of Bcl-x(L) complexes with pro-apoptotic ligands demonstrated the general features of all pro-survival:pro-apoptotic complexes. Structural studies involving Bcl-x(L) were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic. This article will review our current knowledge of the structural biology of Bcl-x(L) and how this has impacted our understanding of the molecular details of the intrinsic apoptotic pathway. MDPI 2019-05-07 /pmc/articles/PMC6540150/ /pubmed/31067648 http://dx.doi.org/10.3390/ijms20092234 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lee, Erinna F.
Fairlie, W. Douglas
The Structural Biology of Bcl-x(L)
title The Structural Biology of Bcl-x(L)
title_full The Structural Biology of Bcl-x(L)
title_fullStr The Structural Biology of Bcl-x(L)
title_full_unstemmed The Structural Biology of Bcl-x(L)
title_short The Structural Biology of Bcl-x(L)
title_sort structural biology of bcl-x(l)
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540150/
https://www.ncbi.nlm.nih.gov/pubmed/31067648
http://dx.doi.org/10.3390/ijms20092234
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