Structural Basis for the Interaction of Fibrin with the Very Low-Density Lipoprotein Receptor Revealed by NMR and Site-Directed Mutagenesis.

ABSTRACT: Interaction of fibrin with the very low-density lipoprotein receptor (VLDLR) promotes transendothelial migration of leukocytes and thereby inflammation. To establish the structural basis for this interaction, we have previously localized the VLDLR-binding site to fibrin βN-domains including fibrin β chain sequence 15-64 and determined the NMR solution structure of the VLDLR(2-4) fragment containing fibrin-binding CR domains 2-4 of VLDLR. In this study, we identified amino acid residues in VLDLR and the βN-domains that are involved in the interaction using NMR and site-directed mutagenesis. The results obtained revealed that Lys47 and Lys53 of the second and third positively charged clusters of the βN-domain, respectively, interact with Trp20 and Asp25 of the CR2 domain and Trp63 and Glu68

SUBMITTER: Gruschus JM 

PROVIDER: S-EPMC10658778 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature