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Review
. 2002 Sep 2;158(5):833-9.
doi: 10.1083/jcb.200206011. Epub 2002 Sep 3.

Integrin activation takes shape

R C Liddington  1 , M H Ginsberg
Affiliations
Review

Integrin activation takes shape

R C Liddington et al. J Cell Biol. .

Abstract

Integrins are cell surface adhesion receptors that are essential for the development and function of multicellular animals. Here we summarize recent findings on the regulation of integrin affinity for ligand (activation), one mechanism by which cells modulate integrin function. The focus is on the structural basis of integrin activation, the role of the cytoplasmic domain in integrin affinity regulation, and potential mechanisms by which activation signals are propagated from integrin cytoplasmic domains to the extracellular ligand-binding domain.

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Figures

Figure 1.
Figure 1.
Speculative model of the initial tertiary and quaternary changes during occupancy of activated integrins that lack an α-I domain. Ligand binding to the MIDAS motif of the β-I domain (M) triggers conformational changes in the three MIDAS loops (numbered 1–3) that cause a shift of helix α1 and MIDAS loop 3 toward the βF-α7 loop (black arrows) and a loosening of the contacts between the β-I domain and the propeller. These movements cause steric clashes that are relieved by a rotation of the β-I domain around the indicated pivot point (red circle) at the hybrid–β-I domain boundary, separating the β-I from the propeller. Helix α7 remains in position, thus freeing itself from its contacts with MIDAS loop 3 and helix α1. That is, there is a net shift of helix α7 with respect to the β-I domain as observed in the α-I domain. Since occupancy activates integrins (Du et al., 1993), a reversal of the order of these events could account for integrin activation. In support of this idea, three mutations (B) shown previously to block activation (Baker et al., 1997) define a path between the movement of MIDAS loop 3 and helix α7; an activation epitope maps to the base of α1 (labeled H) at the β-I–hybrid interface. Red highlighted loops on the propeller map the location of chimeras that switch ligand recognition specificities between integrin αv and α5 subunits.
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