Deciphering RGDechi peptide‐α5β1 integrin interaction mode in isolated cell membranes. Issue 5 (10th April 2018)

• Record Type: Journal Article
• Authors: Russo, Luigi; Farina, Biancamaria; Del Gatto, Annarita; Comegna, Daniela; Di Gaetano, Sonia; Capasso, Domenica; Liguoro, Annamaria; Malgieri, Gaetano; Saviano, Michele; Fattorusso, Roberto; Zaccaro, Laura
• Other Names: Morelli Giancarlo guestEditor.; Rovero Paolo guestEditor.; Toniolo Claudio guestEditor.
• Is Part Of: Peptide science. Volume 110:Issue 5(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-10
• Subjects: cell membrane -- integrin -- NMR -- structure–activity relationship; Peptides -- Periodicals; 572.6505
• DOI: 10.1002/pep2.24065
• Languages: English
• ISSNs: 2475-8817

Abstract

Abstract: Integrins are a large family of heterodimeric receptors critically engaged in pathological processes such as tumor progression and metastasis. Although they are validated therapeutic targets, the molecular determinants governing integrin‐ligand interactions are not yet fully understood, leading to a scarcity of integrin sub‐type exclusive antagonists. In the past decade, we have investigated the biological behavior of the RGDechi, a chimeric peptide able to specifically bind αv β3 integrin without cross reacting with αv β5 and αIIb β3 integrins. Here we have investigated the capability of the peptide to bind α5 β1 integrin and characterized the molecular determinants governing this interaction through a combined experimental and computational approach. The detailed comparison of RGDechi‐α5 β1 structural model with that previously determined of RGDechi in complex with αv β3 shows how the bifunctional nature of the peptide renders the molecule an important tool to recognize integrins with different recognition modalities, providing novel insight on the structural requirements needed to their specific recognition. Abstract :