Structural diversity in integrin/talin interactions.

The adhesion of integrins to the extracellular matrix is regulated by binding of the cytoskeletal protein talin to the cytoplasmic tail of the β-integrin subunit. Structural studies of this interaction have hitherto largely focused on the β3-integrin, one member of the large and diverse integrin fam...

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Auteurs principaux: Anthis, N, Wegener, K, Critchley, DR, Campbell, I
Format: Journal article
Langue:English
Publié: 2010
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author Anthis, N
Wegener, K
Critchley, DR
Campbell, I
author_facet Anthis, N
Wegener, K
Critchley, DR
Campbell, I
author_sort Anthis, N
collection OXFORD
description The adhesion of integrins to the extracellular matrix is regulated by binding of the cytoskeletal protein talin to the cytoplasmic tail of the β-integrin subunit. Structural studies of this interaction have hitherto largely focused on the β3-integrin, one member of the large and diverse integrin family. Here, we employ NMR to probe interactions and dynamics, revealing marked structural diversity in the contacts between β1A, β1D, and β3 tails and the Talin1 and Talin2 isoforms. Coupled with analysis of recent structures of talin/β tail complexes, these studies elucidate the thermodynamic determinants of this heterogeneity and explain why the Talin2/β1D isoforms, which are co-localized in striated muscle, form an unusually tight interaction. We also show that talin/integrin affinity can be enhanced 1000-fold by deleting two residues in the β tail. Together, these studies illustrate how the integrin/talin interaction has been fine-tuned to meet varying biological requirements.
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spelling oxford-uuid:510bc0b2-2e9e-4964-84ba-595c16cba7982022-03-26T16:17:11ZStructural diversity in integrin/talin interactions.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:510bc0b2-2e9e-4964-84ba-595c16cba798EnglishSymplectic Elements at Oxford2010Anthis, NWegener, KCritchley, DRCampbell, IThe adhesion of integrins to the extracellular matrix is regulated by binding of the cytoskeletal protein talin to the cytoplasmic tail of the β-integrin subunit. Structural studies of this interaction have hitherto largely focused on the β3-integrin, one member of the large and diverse integrin family. Here, we employ NMR to probe interactions and dynamics, revealing marked structural diversity in the contacts between β1A, β1D, and β3 tails and the Talin1 and Talin2 isoforms. Coupled with analysis of recent structures of talin/β tail complexes, these studies elucidate the thermodynamic determinants of this heterogeneity and explain why the Talin2/β1D isoforms, which are co-localized in striated muscle, form an unusually tight interaction. We also show that talin/integrin affinity can be enhanced 1000-fold by deleting two residues in the β tail. Together, these studies illustrate how the integrin/talin interaction has been fine-tuned to meet varying biological requirements.
spellingShingle Anthis, N
Wegener, K
Critchley, DR
Campbell, I
Structural diversity in integrin/talin interactions.
title Structural diversity in integrin/talin interactions.
title_full Structural diversity in integrin/talin interactions.
title_fullStr Structural diversity in integrin/talin interactions.
title_full_unstemmed Structural diversity in integrin/talin interactions.
title_short Structural diversity in integrin/talin interactions.
title_sort structural diversity in integrin talin interactions
work_keys_str_mv AT anthisn structuraldiversityinintegrintalininteractions
AT wegenerk structuraldiversityinintegrintalininteractions
AT critchleydr structuraldiversityinintegrintalininteractions
AT campbelli structuraldiversityinintegrintalininteractions