Structural Insights Into Complement Inhibition: Visualizing Distinct Binding Modes of C4b-Binding Protein Complexes With C4b and SAP.

ABSTRACT: C4b-binding protein (C4BP) is an innate immune inhibitor found in serum. Human C4BP adopts spider-like higher-order structures (HOS) formed by disulfide-linked C4BPα and C4BPβ chains that non-covalently bind vitamin K-dependent protein S (ProS). These spider-like structures can form even larger complexes as C4BP interacts with other, mostly complement-related, proteins. The complement inhibitory role of C4BP is primarily mediated through its interaction with C4b. C4BP also binds with high affinity to serum amyloid P component (SAP), a pentraxin family member associated with amyloidosis conditions. Here, we structurally and compositionally characterize C4BP interactions with these two natively occurring binders. To achieve this, we combine mass photometry, high-speed atomic force microscopy

SUBMITTER: Kadava T 

PROVIDER: S-EPMC12419116 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature