Crystal structure of the extracellular segment of integrin {alpha}V{beta}3 in complex with an Arg-Gly-Asp ligand.
The structural basis for the divalent cation-dependent binding of heterodimeric alpha beta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alpha Vbeta 3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alpha V and beta 3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in beta A, the ligand-binding domain of beta 3; in the complex, beta A acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alpha V relative to beta 3.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC); National Institutes of Health (NIH)
- DOE Contract Number:
- DE-AC02-06CH11357
- OSTI ID:
- 949515
- Report Number(s):
- ANL/BIO/JA-41660; SCEHDK; TRN: US201012%%303
- Journal Information:
- Science, Vol. 296, Issue 5565 ; Apr. 5, 2002; ISSN 0193-4511
- Country of Publication:
- United States
- Language:
- ENGLISH
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Crystal structure of the extracellular segment of integrin {alpha}V{beta}3.
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