Dynamic behaviour of ubiquitin receptor S5a in free and complex with K48-linked diubiquitin

Abstract

S5a is a critical component of proteasome and carries ubiquitin recognition function. Previous nuclear magnetic resonance (NMR) experiments have shown that K48-linked diubiquitin binds to S5a through a major and a minor conformational species. Molecular dynamics simulations have been performed on S5a and S5a:K48-linked diubiquitin complex extracted from both species to investigate the essential dynamic behaviour of the receptor S5a in free and complex with the diubiquitin. It shows that structures of S5a as well as S5a:diubiquitin complex are very mobile during the simulations, which enables the receptor to undergo a conformational interconversion from the minor to major species or vice versa, though finally the receptor alone tends to adopt a tight packed structure. The binding of diubiquitin to S5a reduces the structural mobility of the receptor, however, it is still able to cover the different conformations within each species of the complex. Despite the high mobility of the structures, the binding of ubiquitin interacting with motif 2 (UIM2) is always stronger than the UIM1 to the ubiquitin subunit. Accordingly, the current dynamic study provides a vivid view how the receptor in free and complex with diubiquitin sampled the multiple conformations as well as their exchanges revealed in two NMR structures.