Interaction of Human C5a with the Major Peptide Fragments of C5aR1: Direct Evidence in Support of "Two-Site" Binding Paradigm.

ABSTRACT: The C5a receptor's (C5aR1) physiological function in various tissues depends on its high-affinity binding to the cationic proinflammatory glycoprotein C5a, produced during the activation of the complement system. However, an overstimulated complement can quickly alter the C5a-C5aR1 function from physiological to pathological, as has been noted in the case of several chronic inflammation-induced diseases like asthma, lung injury, multiorgan failure, sepsis, and now COVID-19. In the absence of the structural data, the current study provides the confirmatory biophysical validation of the hypothesized "two-site" binding interactions of C5a, involving (i) the N-terminus (NT) peptide ("Site1") and (ii) the extracellular loop 2 (ECL2) peptide of the extracellular surface (ECS) of the C5aR1 ("Site

SUBMITTER: Das A 

PROVIDER: S-EPMC8427777 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature