Crystal Structure of the Extracellular Segment of Integrin αVβ3 in Complex with an Arg-Gly-Asp Ligand

  title={Crystal Structure of the Extracellular Segment of Integrin $\alpha$V$\beta$3 in Complex with an Arg-Gly-Asp Ligand},
  author={Jian-ping Xiong and Thilo Stehle and Rongguang Zhang and Andrzej J Joachimiak and Matthias Frech and Simon L. Goodman and M. Amin Arnaout},
  pages={151 - 155}
The structural basis for the divalent cation–dependent binding of heterodimeric αβ 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 αVβ3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major… 
Structure-Function Analysis of Arg-Gly-Asp Helix Motifs in αvβ6 Integrin Ligands*
It is shown that 20-mer peptide ligands, derived from high affinity ligands of αvβ6, have a common structure comprising an Arg-Gly-Asp motif at the tip of a hairpin turn followed immediately by a C-terminal helix.
Structure of an Integrin-Ligand Complex Deduced from Solution X-ray Scattering and Site-directed Mutagenesis*
The structural basis of the interaction of integrin heterodimers with their physiological ligands is poorly understood. We have used solution x-ray scattering to visualize the head region of integrin
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  • Chemistry, Biology
    Proceedings of the National Academy of Sciences
  • 2014
High-resolution crystal structures and results directly demonstrate that Ca2+ binding to the ADMIDAS stabilizes integrins in the low-affinity, closed conformation.
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Structural determinants of integrin β-subunit specificity for latent TGF-β
Variation in a pair of single key residues in SDL1 and SDL3 correlates with the variation of the entire β subunit in integrin evolution, thus suggesting a paradigmatic role in overall β-subunit function.
Coming to grips with integrin binding to ligands.
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The AGDV tetrapeptide from KQAGDV binds to the αIIbβ3 headpiece with affinity comparable with the RGDSP peptide from fibronectin, and is found to have very little contact with the α-subunit.


An Isoleucine-based Allosteric Switch Controls Affinity and Shape Shifting in Integrin CD11b A-domain*
These data establish the structure-function correlates for the CD11b A-domain, and define a ligand-independent isoleucine-based allosteric switch intrinsic to this domain that controls its conformation and affinity.
Locking in alternate conformations of the integrin αLβ2 I domain with disulfide bonds reveals functional relationships among integrin domains
Results suggest that Mn2+ activates αLβ2 by binding to a site other than the I domain, most likely the I-like domain of β2, and indirectly contributes to ligand binding by regulating opening of the Idomain in wild-type αL β2.
Identification of a regulatory region of integrin beta 1 subunit using activating and inhibiting antibodies.
A small region of beta 1 subunit (residues 207-218) is identified that is critical for the binding of both activating and inhibiting monoclonal antibodies against human beta 1 using interspecies chimeric beta 1 and site-directed mutagenesis.
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  • A. Qu, D. Leahy
  • Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
The 1.8-A crystal structure of the CD11a I-domain with bound manganese ion reveals a strained hydrophobic ridge adjacent to the bound metal ion that may serve as a ligand-binding surface and is likely to rearrange in the absence of bound metal ions.