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...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/96439 http://hdl.handle.net/10220/9896 |
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| author | Chua, Geok-Lin Patra, Alok Tanala Tan, Suet Mien Bhattacharjya, Surajit |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Chua, Geok-Lin Patra, Alok Tanala Tan, Suet Mien Bhattacharjya, Surajit |
| author_sort | Chua, Geok-Lin |
| collection | NTU |
| 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. |
| first_indexed | 2024-10-01T06:58:46Z |
| format | Journal Article |
| id | ntu-10356/96439 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:58:46Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-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 |
| 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 |
| title | 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_short | 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 |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/96439 http://hdl.handle.net/10220/9896 |
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