Medical College of Wisconsin
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Modulation of integrin activation and signaling by α1/α1'-helix unbending at the junction. J Cell Sci 2013 Dec 15;126(Pt 24):5735-47

Date

10/23/2013

Pubmed ID

24144695

DOI

10.1242/jcs.137828

Scopus ID

2-s2.0-84890487402 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

How conformational signals initiated from one end of the integrin are transmitted to the other end remains elusive. At the ligand-binding βI domain, the α1/α1'-helix changes from a bent to a straightened α-helical conformation upon integrin headpiece opening. We demonstrated that a conserved glycine at the α1/α1' junction is crucial for maintaining the bent conformation of the α1/α1'-helix in the resting state. Mutations that facilitate α1/α1'-helix unbending rendered integrin constitutively active; however, mutations that block the α1/α1'-helix unbending abolished soluble ligand binding upon either outside or inside stimuli. Such mutations also blocked ligand-induced integrin extension from outside the cell, but had no effect on talin-induced integrin extension from inside the cell. In addition, integrin-mediated cell spreading, F-actin stress fiber and focal adhesion formation, and focal adhesion kinase activation were also defective in these mutant integrins, although the cells still adhered to immobilized ligands at a reduced level. Our data establish the structural role of the α1/α1' junction that allows relaxation of the α1/α1'-helix in the resting state and transmission of bidirectional conformational signals by helix unbending upon integrin activation.

Author List

Zhang C, Liu J, Jiang X, Haydar N, Zhang C, Shan H, Zhu J

Author

Jieqing Zhu PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Amino Acid Substitution
Animals
CHO Cells
Cell Adhesion
Cricetinae
Cricetulus
Fibrinogen
HEK293 Cells
Humans
Integrin beta Chains
Ligands
Molecular Sequence Data
Mutagenesis, Site-Directed
Protein Binding
Protein Structure, Secondary
Signal Transduction