GA/GB fold switching may modulate fatty acid transfer from human serum albumin to bacteria

Abstract

Human serum albumin (HSA) accounts for most of the functions of plasma. Among others, HSA serves as a carrier and a solubilizer for many endogenous and exogenous ligands, including fatty acids (FAs) as well as peptides and proteins such as the GA module of the bacterial poly(A)-binding (PAB) protein. Although the biological function(s) of the GA module of the bacterial PAB protein is unknown, the acquisition of the GA module adds selective advantages to the bacterium in terms of growth rate and increase in virulence, probably by providing the bacteria with FAs and, possibly, other nutrients transported by HSA. Here, we hypothesize that the GA module may undergo a structural transition from the all-α form to the 4β+α form typical of the GB domains upon binding of a FA molecule, as part of the mechanism which allows the bacterial PAB protein to extract FAs from HSA.