Three-dimensional EM structure of the ectodomain of integrin αVβ3 in a complex with fibronectin

Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 04/2005; 168(7):1109-18. DOI: 10.1083/jcb.200410068
Source: PubMed


Integrins are alphabeta heterodimeric cell surface receptors that mediate transmembrane signaling by binding extracellular and cytoplasmic ligands. The ectodomain of integrin alphaVbeta3 crystallizes in a bent, genuflexed conformation considered to be inactive (unable to bind physiological ligands in solution) unless it is fully extended by activating stimuli. We generated a stable, soluble complex of the Mn(2+)-bound alphaVbeta3 ectodomain with a fragment of fibronectin (FN) containing type III domains 7 to 10 and the EDB domain (FN7-EDB-10). Transmission electron microscopy and single particle image analysis were used to determine the three-dimensional structure of this complex. Most alphaVbeta3 particles, whether unliganded or FN-bound, displayed compact, triangular shapes. A difference map comparing ligand-free and FN-bound alphaVbeta3 revealed density that could accommodate the RGD-containing FN10 in proximity to the ligand-binding site of beta3, with FN9 just adjacent to the synergy site binding region of alphaV. We conclude that the ectodomain of alphaVbeta3 manifests a bent conformation that is capable of stably binding a physiological ligand in solution.

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Available from: M. Amin A Arnaout, Dec 03, 2015
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    • "This model is inadequate to explain the propagation of conformational changes from the cytoplasmic tails to the integrin head. On the other hand, this model assumes ligand binding is possible only when integrins are in an extended, high-affinity conformation, whereas studies have shown soluble avb3 molecules bound to fibronectin maintain their bent conformation (Adair et al., 2005). "
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