Folding and Binding Properties of Human Complement Receptor Type 1 Extracellular Domain

Abstract

Complement receptor type 1 (CR1 or CD35) is a peripheral glycosylated membrane protein that regulates the complement activation in the control of immune responses. The author would like to overview the folding and binding properties of the soluble form of CR1, so-called as sCR1, introducing our development of the high-yield overexpression and purification methods as well as the investigation to its molecular structure. Although sCR1 prepared through our method showed the highest binding affinity against C3b, it is quite difficult to be crystallized for X-ray structure analysis. In spite of many attempts, only microcrystals have been obtained so far. Considering the usefulness to understand factors within the difficulty, the primary sequence of sCR1 has been reexamined from the viewpoints both of secondary structure predictions and recent findings of intrinsically disordered proteins (IDPs) or natively unfolded proteins (NUPs). As an example, the theoretically predicted structure of a short consensus repeat (SCR) of a binding domain, SCR-15-17 in sCR1 is compared with the reported solution structure by NMR. The discussion is extended to protein structure studies with proteins containing ID regions, which are unfolded state without taking uniformly decided structures.