Crystal structure of α5β1 integrin ectodomain: Atomic details of the fibronectin receptor

Abstract

The crystal structure of the α5β1 integrin reveals conformational changes and amino acids important for ligand binding.

Leukocyte integrin α L β 2 headpiece structures: The αI domain, the pocket for the internal ligand, and concerted movements of its loops

“…1C). The LFA-1 βI domain β1-α1 loop, α1-helix, β6-α7 loop, and α7-helix have conformations essentially identical to those in closed β1, β3, β6, and β7 integrin structures (19)(20)(21)(22)(23).…”

An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation

“…The ␤1 integrin heterodimerizes with one of 12 possible ␣ subunits and mediates adhesion, spreading, and migration on multiple ligands, including collagen, laminin, and fibronectin (47,48). A recent study on the crystal structure of ␣5␤1 ectodomain showed that the RGD-binding pocket is surrounded by several N-glycan chains, leaving an exposed surface along the subunit interface (49). Computer modeling also showed that sialylation on an I-like domain may affect the signaling mediated by integrins (44).…”

Protein conformation as a regulator of cell–matrix adhesion

“…Please note the synergy site interactions between the a-subunit (D154) and FN type III repeat 9 (R1379). 48 Fig . 1E shows the C-terminal fibrinogen peptide bound to the open and extended form of aIIbb3.…”

“…In addition to the influence of ligand-binding and di-valent cations on the conformational equilibrium of micelle embedded integrins, 6 application of tensional forces along the ECM-actin axis induces a catch-bond behavior, 47 thus further stabilizing integrin-ligand interaction and force bearing. Although still incompletely understood, the catch-bond mechanism is likely connected to an approximately 200-fold increase in ligand-binding affinity due to hybrid-domain swing-out, 7 and this open conforma- additional interactions between the synergy site residue R1376 of FN and of D154 of the integrin a-subunit enhance the on-rate of binding 48,49 ( Fig. 1).…”

“…53 The integrin structure in panel B corresponds to a5b1 (PDB 3VI4), containing bound RGD peptide. 48 Panel C is a chimeric structure created by joining the a5-chain from PDB 3VI4 (B) and b3-chain and ligand from PDB 2VDO (aIIbb3, E). 50 The chimeric structure (panel C) was obtained by aligning the two b-propeller domains using Swiss PDB viewer (http://www.expasy.org/spdbv/).…”