The crystal structure of the plexin-semaphorin-integrin domain/hybrid domain/I-EGF1 segment from the human integrin β2 subunit at 1.8-Å resolution

Min Long Shi, Kumar Sundramurthy, Bin Liu, Suet Mien Tan, S. K.Alex Law, Julien Lescar

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Integrins are modular (αβ) heterodimeric proteins that mediate cell adhesion and convey signals across the plasma membrane. Interdomain motions play a key role in signal transduction by propagating structural changes through the molecule, thus controlling the activation state and adhesive properties of the integrin. We expressed a soluble fragment of the human integrin β2 subunit comprising the plexin-semaphorin-integrin domain (PSI)/hybrid domain/I-EGF1 fragment and present its crystal structure at 1.8-Å resolution. The structure reveals an elongated molecule with a rigid architecture stabilized by nine disulfide bridges. The PSI domain is located centrally and participates in the formation of extended interfaces with the hybrid domain and I-EGF1 domains, respectively. The hybrid domain/PSI interface involves the burial of an Arg residue, and contacts between PSI and I-EGF1 are mainly mediated by well conserved Arg and Trp residues. Conservation of key interacting residues across the various integrin β subunits sequences suggests that our structure represents a good model for the entire integrin family. Superposition with the integrin β3 receptor in its bent conformation suggests that an articulation point is present at the linkage between its I-EGF1 and I-EGF2 modules and underlines the importance of this region for the control of integrin-mediated cell adhesion.

Original languageEnglish (US)
Pages (from-to)30586-30593
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number34
DOIs
StatePublished - Aug 26 2005
Externally publishedYes

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