NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin

Integrins are a group of transmembrane signaling proteins that are important in biological processes such as cell adhesion, proliferation and migration. Integrins are α/β hetero-dimers and there are 24 different integrins formed by specific combinations of 18 α and 8 β subunits in humans. Generall...

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Main Authors: Chua, Geok-Lin, Patra, Alok Tanala, Tan, Suet Mien, Bhattacharjya, Surajit
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/96439
http://hdl.handle.net/10220/9896
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-964392023-02-28T17:04:20Z NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin Chua, Geok-Lin Patra, Alok Tanala Tan, Suet Mien Bhattacharjya, Surajit School of Biological Sciences DRNTU::Science::Biological sciences Integrins are a group of transmembrane signaling proteins that are important in biological processes such as cell adhesion, proliferation and migration. Integrins are α/β hetero-dimers and there are 24 different integrins formed by specific combinations of 18 α and 8 β subunits in humans. Generally, each of these subunits has a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). CTs of integrins are important in bidirectional signal transduction and they associate with a large number of intracellular proteins. Principal Findings: Using NMR spectroscopy, we determined the 3-D structure of the full-length α4 CT (Lys968-Asp999) and characterize its interactions with the adaptor protein paxillin. The α4 CT assumes an overall helical structure with a kink in its membrane proximal region. Residues Gln981-Asn997 formed a continuous helical conformation that may be sustained by potential ionic and/or hydrogen bond interactions and packing of aromatic-aliphatic side-chains. 15N-1H HSQC NMR experiments reveal interactions of the α4 CT C-terminal region with a fragment of paxillin (residues G139-K277) that encompassed LD2-LD4 repeats. Residues of these LD repeats including their adjoining linkers showed α4 CT bindinginduced chemical shift changes. Furthermore, NMR studies using LD-containing peptides showed predominant interactions between LD3 and LD4 of paxillin and α4 CT. Docked structures of the α4 CT with these LD repeats suggest possible polar and/or salt-bridge and non-polar packing interactions. Significance: The current study provides molecular insights into the structural diversity of α CTs of integrins and interactions of integrin α4 CT with the adaptor protein paxillin. Published version 2013-05-07T06:13:21Z 2019-12-06T19:30:51Z 2013-05-07T06:13:21Z 2019-12-06T19:30:51Z 2013 2013 Journal Article Chua, G. L., Patra, A. T., Tan, S. M., & Bhattacharjya, S. (2013). NMR Structure of Integrin α4 Cytosolic Tail and Its Interactions with Paxillin. PLoS ONE, 8(1). 1932-6203 https://hdl.handle.net/10356/96439 http://hdl.handle.net/10220/9896 10.1371/journal.pone.0055184 23383101 en PLoS ONE © 2013 The Author(s). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Chua, Geok-Lin
Patra, Alok Tanala
Tan, Suet Mien
Bhattacharjya, Surajit
NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin
description Integrins are a group of transmembrane signaling proteins that are important in biological processes such as cell adhesion, proliferation and migration. Integrins are α/β hetero-dimers and there are 24 different integrins formed by specific combinations of 18 α and 8 β subunits in humans. Generally, each of these subunits has a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). CTs of integrins are important in bidirectional signal transduction and they associate with a large number of intracellular proteins. Principal Findings: Using NMR spectroscopy, we determined the 3-D structure of the full-length α4 CT (Lys968-Asp999) and characterize its interactions with the adaptor protein paxillin. The α4 CT assumes an overall helical structure with a kink in its membrane proximal region. Residues Gln981-Asn997 formed a continuous helical conformation that may be sustained by potential ionic and/or hydrogen bond interactions and packing of aromatic-aliphatic side-chains. 15N-1H HSQC NMR experiments reveal interactions of the α4 CT C-terminal region with a fragment of paxillin (residues G139-K277) that encompassed LD2-LD4 repeats. Residues of these LD repeats including their adjoining linkers showed α4 CT bindinginduced chemical shift changes. Furthermore, NMR studies using LD-containing peptides showed predominant interactions between LD3 and LD4 of paxillin and α4 CT. Docked structures of the α4 CT with these LD repeats suggest possible polar and/or salt-bridge and non-polar packing interactions. Significance: The current study provides molecular insights into the structural diversity of α CTs of integrins and interactions of integrin α4 CT with the adaptor protein paxillin.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Chua, Geok-Lin
Patra, Alok Tanala
Tan, Suet Mien
Bhattacharjya, Surajit
format Article
author Chua, Geok-Lin
Patra, Alok Tanala
Tan, Suet Mien
Bhattacharjya, Surajit
author_sort Chua, Geok-Lin
title NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin
title_short NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin
title_full NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin
title_fullStr NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin
title_full_unstemmed NMR structure of integrin α4 cytosolic tail and Its interactions with paxillin
title_sort nmr structure of integrin α4 cytosolic tail and its interactions with paxillin
publishDate 2013
url https://hdl.handle.net/10356/96439
http://hdl.handle.net/10220/9896
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