Conformational dependence of integrin‐binding peptides derived from homologous loop regions in the laminin α chains. (3rd September 2020)

• Record Type: Journal Article
• Authors: Ishikawa, Masaya; Hamada, Keisuke; Yamada, Yuji; Kumai, Jun; Katagiri, Fumihiko; Kikkawa, Yamato; Nomizu, Motoyoshi
• Is Part Of: Journal of peptide science. Volume 26:Number 12(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-09-03
• Subjects: cell attachment -- cyclic peptide -- integrin -- laminin; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3284
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Laminin α chains (α1–α5 chains) are expressed in a tissue‐ and developmental stage‐specific manner and have diverse chain‐specific biological functions. Especially, laminin globular (LG) modules (LG1–LG5) located at the C‐terminus of the α chains play a critical role in the biological activities of laminins. Each LG module is composed of a 14‐stranded β‐sheet (A‐N) sandwich structure. We previously screened cell attachment activity of the loop regions between the E and F strands in the LG modules using 17 homologous peptides (EF peptides) and found that four active EF peptides bind to integrin α2β1. One of the four peptides, G4EF1 demonstrated improved cell attachment activity when cyclized. Here, we focused on the remaining three integrin α2β1‐binding EF peptides (G5EF1, G3EF3, and G5EF5) and analyzed the relationship between their peptide conformation and cell attachment activity. First, we determined their active core sequences and found that G5EF1z (IGLEIVDGKVLFHVNN), G3EF3z (LLVTLEDGHIALST), and G5EF5z (KVLTEQVL) are the core sequences. Cyclic peptides of the core sequences (cycloG5EF1z, cycloG3EF3z, and cycloG5EF5z) enhanced integrin‐mediated cell adhesion activity compared with their linear peptides. The results indicated that cell adhesion activity of the integrin α2β1‐binding EF peptides is conformation dependent and that the loop structure is critical for their activity. This suggests that conformation of the loop regions plays an important role for the activities of the LG modules. Abstract : Three peptides (G5EF1, G3EF3, and G5EF5) derived from EF loop regions of laminin α chain LG modules have been reported to promote cell adhesion via integrin α2β1. In this study, we investigated conformational dependence of the three EF sequences using their linear and cyclic peptides. The cyclic peptides exhibited higher cell adhesion activity than linear forms, indicating importance of loop structure to the EF peptides.