Cleavage, Downregulation, and Aggregation of Serum Amyloid A.

ABSTRACT: Various diseases cause overexpression of the serum amyloid A (SAA) protein, which in some cases, but not in all cases, leads to amyloidosis as a secondary disease. Response to the overexpression involves dissociation of the SAA hexamer and subsequent cleavage of the released monomers, most commonly yielding fragments SAA_1-76 of the full-sized SAA_1-104. We report results from molecular dynamic simulations that probe the role of this cleavage for downregulating the activity and concentration of SAA. We propose a mechanism that relies on two elements. First, the probability to assemble into hexamers is lower for the fragments than it is for the full-sized protein. Second, unlike other fragments, SAA_1-76 can switch between two distinct configurations. The first

SUBMITTER: Wang W 

PROVIDER: S-EPMC7346682 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature