Rational engineering of a minimized immune inhibitor with unique triple-targeting properties.

ABSTRACT: Inadequate control of the complement system is the underlying or aggravating factor in many human diseases. Whereas treatment options that specifically target the alternative pathway (AP) of complement activation are considered highly desirable, no such option is available in the clinic. In this study, we present a successful example of protein engineering, guided by structural insight on the complement regulator factor H (FH), yielding a novel complement-targeted therapeutic (mini-FH) with clinical potential. Despite a 70% reduction in size, mini-FH retained and in some respects exceeded the regulatory activity and cell surface-recognition properties of its parent protein FH, including the recently described recognition of sites of oxidative stress. Importantly, the chosen design extended

SUBMITTER: Schmidt CQ 

PROVIDER: S-EPMC3825029 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature