Structural specializations of α4β7, an integrin that mediates rolling adhesion

Abstract

Electron microscopy and crystallography studies of α4β7 integrin reveal the mechanism by which this atypical integrin enables rolling adhesion prior to integrin activation.

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).…”

Modulation of integrin activation and signaling by α1/α1′-helix unbending at the junction

“…2A). Crystal structure analyses of b3, b1, b2 and b7 integrins at the closed headpiece conformation all revealed a bent conformation of the a1/a19-helix (Xie et al, 2010;Zhu et al, 2010;Nagae et al, 2012;Yu et al, 2012) (Fig. 2B).…”

“…For example, a4b7 integrin mediates both cell rolling and firm adhesion on its MadCAM-1 (mucosal adhesion molecule-1) ligands Berlin et al, 1995). It was suggested that the rolling adhesion was mediated by the closed or intermediate headpiece conformation that is intermediate affinity, while the firm adhesion was mediated by the open headpiece conformation that is high affinity Yu et al, 2012). Crystal soaking studies already revealed the separability of the movements of the b1-a1 loop and the a1/a19-helix (Xiong et al, 2002;Nagae et al, 2012;Zhu et al, 2013).…”

The Unique Disulfide Bond-stabilized W1 β4-β1 Loop in the α4 β-Propeller Domain Regulates Integrin α4β7 Affinity and Signaling

“…The crevice running along the ␣-␤ subunit in ␣ 4 ␤ 7 ligand-binding site is longer, wider, and deeper than those in ␣ V ␤ 3 , ␣ IIb ␤ 3 , and ␣ 5 ␤ 1 , which is contributed largely by the loops on the face of the ␤-propeller domain that bind the ␤I domain and form the ligand-binding site (28). Among the loops, the W1 ␤4-␤1 loop is unique, as it contains a disulfide bond existing only in the integrin ␣ 4 /␣ 9 subfamily.…”

“…As shown from the crystal structure of the ␣ 4 ␤ 7 headpiece, the ␤-propeller domain of ␣ 4 differs from those of the previously characterized ␣ IIb , ␣ V , and ␣ X integrins, especially in the loops on the face of ␤-propeller domain that bind the ␤I domain and contribute to the formation of the ␣ 4 ␤ 7 ligand-binding pocket (28) (Fig. 1A).…”