Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity.

ABSTRACT: The plasma protein C3 is a central element in the activation and effector functions of the complement system. A hereditary dysfunction of C3 that prevents complement activation via the alternative pathway (AP) was described previously in a Swedish family, but its genetic cause and molecular consequences have remained elusive. In this study, we provide these missing links by pinpointing the dysfunction to a point mutation in the β-chain of C3 (c.1180T > C; p.Met(373)Thr). In the patient's plasma, AP activity was completely abolished and could only be reconstituted with the addition of normal C3. The M373T mutation was localized to the macroglobulin domain 4 of C3, which contains a binding site for the complement inhibitor compstatin and is considered critical for the interaction of C3 with

SUBMITTER: Sfyroera G 

PROVIDER: S-EPMC4369434 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature