Modeling of phosphorylated forms of complement system factors C4 and CFB.

Abstract

Kidney cancer ranks as the 14th most common cancer worldwide. Despite its heterogeneity, it often presents with clinical manifestations similar to other renal diseases, which complicates timely diagnosis. Many types of malignant renal neoplasms can mimic benign processes, and some tumors can develop asymptomatically until the late stages of the disease. Our research focuses on modeling complement C4 and CFB proteoforms, which are of interest for understanding the molecular basis of pathogenesis for common kidney diseases: kidney calculi, kidney cysts, and malignant neoplasms of the kidney. In this work, we performed an analysis of the stability and interface characterization of these proteins in complexes with their natural binding partners using molecular dynamics methods. We have demonstrated that the phosphorylation sites of complement factors C4 125TPO and CFB 161SEP are localized at the binding interface with their natural partners. This modification likely modulates protein function, as we have identified local effects in the vicinity of the modification site. In protein complexes, we observe a redistribution of energetic contributions among the interacting amino acid residues at the interface.