Conformational resemblance between the structures of integrin-activating pentapetides derived from betaig-h3 and RGD peptide analogues in a membrane environment.
The peptides NKDIL and EPDIM, respectively derived from the 2nd and 4th domains of betaig-h3, were fully active in mediating cell adhesion through interactions with alpha3beta1 integrin [Biochem. Biophys. Res. Commun. 294 (2002) 940; J. Biol. Chem. 275 (2000) 30907]. Here, the conformational differences between NKDIL and EPDIM in water and in membrane environments were studied using CD spectroscopy, and their structures in sodium dodecylsulfate micelles were determined by NMR. The two peptides adopt beta-turn structures like RGD peptides, and have more regular structures in micelles than in aqueous buffers. EPDIM shows a distorted type I beta-turn for the PDIM segment in a membrane environment. The structure of NKDIL is similar with the standard type I' beta-turn, but shows large backbone flexibility even in a membrane environment. The conformational change of the 4th repeated domain of betaig-h3 in micelle solutions suggests that the Asp-Ile motif of the 4th fas-1 domain (EPDIM) would be solvent-exposed and could interact with integrin alpha3beta1 in a membrane environment. The present study provides a structural basis of betaig-h3 function and information for the development of integrin-regulating drugs involving the wound healing protein.
Park
Sung Jean
SJ
National Research Laboratory (MPS), College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Park
Sangho
S
Ahn
Hee-Chul
HC
Kim
In-San
IS
Lee
Bong-Jin
BJ
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002942:Circular Dichroism; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism; D016023:Integrins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary
D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1; D016023:Integrins; D008823:Micelles; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid