Dataset Information

Molecular Basis of the Ligand Binding Specificity of ?v?8 Integrin.

ABSTRACT: ?v?8 is an integrin that recognizes an Arg-Gly-Asp (RGD) motif and interacts with fibronectin, vitronectin, and latent TGF-?1. We comprehensively determined the binding activity of the ?v?8 integrin toward 25 secreted proteins having an RGD motif. The ?v?8 integrin strongly bound to latent TGF-?1 but showed marginal activity for other RGD-containing proteins, including fibronectin and vitronectin. Site-directed mutagenesis of latent TGF-?1 demonstrated that the high affinity binding of ?v?8 integrin to latent TGF-?1 was defined by Leu-218 immediately following the RGD motif within the latency-associated peptide of TGF-?1. Consistent with the critical role of Leu-218 in latent TGF-?1 recognition by ?v?8 integrin, a 9-mer synthetic peptide containing an RGDL sequence strongly inhibited interactions of latent TGF-?1 with ?v?8 integrin, whereas a 9-mer peptide with an RGDA sequence was ?60-fold less inhibitory. Because ?v?3 integrin did not exhibit strong binding to latent TGF-?1 or distinguish between RGDL- and RGDA-containing peptides, we explored the mechanism by which the integrin ?8 subunit defines the high affinity binding of latent TGF-?1 by ?v?8 integrin. Production of a series of swap mutants of integrin ?8 and ?3 subunits indicated that the high affinity binding of ?v?8 integrin with latent TGF-?1 was ensured by interactions between the Leu-218 residue and the ?8 I-like domain, with the former serving as an auxiliary recognition residue defining the restricted ligand specificity of ?v?8 integrin toward latent TGF-?1. In support of this conclusion, high affinity binding toward the ?v?8 integrin was conferred on fibronectin by substitution of its RGDS motif with an RGDL sequence.

SUBMITTER: Ozawa A

PROVIDER: S-EPMC4882426 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Molecular Basis of the Ligand Binding Specificity of αvβ8 Integrin.

Ozawa Akio A Sato Yuya Y Imabayashi Tsukasa T Uemura Toshihiko T Takagi Junichi J Sekiguchi Kiyotoshi K

The Journal of biological chemistry 20160331 22

αvβ8 is an integrin that recognizes an Arg-Gly-Asp (RGD) motif and interacts with fibronectin, vitronectin, and latent TGF-β1. We comprehensively determined the binding activity of the αvβ8 integrin toward 25 secreted proteins having an RGD motif. The αvβ8 integrin strongly bound to latent TGF-β1 but showed marginal activity for other RGD-containing proteins, including fibronectin and vitronectin. Site-directed mutagenesis of latent TGF-β1 demonstrated that the high affinity binding of αvβ8 inte ...[more]

PMID: 27033701

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Dataset Information

Molecular Basis of the Ligand Binding Specificity of ?v?8 Integrin.

Publications

Molecular Basis of the Ligand Binding Specificity of αvβ8 Integrin.

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