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Review
. 2006 Oct;18(5):579-86.
doi: 10.1016/j.ceb.2006.08.005. Epub 2006 Aug 14.

Integrin structures and conformational signaling

Bing-Hao Luo  1 , Timothy A Springer
Affiliations
Review

Integrin structures and conformational signaling

Bing-Hao Luo et al. Curr Opin Cell Biol. 2006 Oct.

Abstract

Integrins are cell adhesion molecules that play critical roles in development, wound healing, hemostasis, immunity and cancer. Advances in the past two years have shed light on the structural basis for integrin regulation and signaling, especially on how global conformational changes between bent and extended conformations relate to the inter-domain and intra-domain shape shifting that regulates affinity for ligand. The downward movements of the C-terminal helices of the alpha I and beta I domains and the swing-out of the hybrid domain play pivotal roles in integrin conformational signaling. Experiments have also shown that integrins transmit bidirectional signals across the plasma membrane by coupling extracellular conformational change with an unclasping and separation of the alpha and beta transmembrane and cytoplasmic domains.

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Figures

Figure 1
Figure 1
Integrin architecture and conformational changes associated with affinity regulation. (a) Organization of domains within the primary structures. (b,c) Conformational change of integrins lacking an I domain (b) or containing an α I domain (c). The domains are shown with the same color scheme as in (a).
Figure 2
Figure 2
Conformational regulation in integrin headpiece domains. (a) Overview of the movements of the β I, hybrid, and PSI domains. Non-moving segments of the β I backbone are shown as a grey worm. Moving segments are color-coded. The downward movement of the α7 helix is coupled to the swing-out of the hybrid domain, which in turn plays a critical role in transmitting signals between the ligand-binding headpiece and the integrin legs. (b) Conformational change of the α I domain. Non-moving segments of the backbone are shown as a grey worm. The moving segments, shown as Cα-traces, of the closed (gold) and open (cyan) αM I domains and their MIDAS metal ions are shown, and direction of movement is shown with arrows. The downward movement of the α7 helix plays a critical role in transmitting signals between the α I domain and the β I domain.
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