Hazards of compression treatment of the leg: an estimate from Scottish surgeons.

TLDR

Hsp110 proteins act as nucleotide exchange factors for Hsp70s and serve as chaperones, yet their domain communication and functions remain poorly understood despite structural similarity to Hsp70s. The authors aimed to characterize the atypical domain communication of yeast Hsp110 Sse1. They employed single‑molecule FRET, small‑angle X‑ray scattering, and molecular dynamics simulations to probe Sse1’s structure. Sse1 lacks the typical Hsp70 domain movements, instead undergoing unique structural changes upon nucleotide and substrate binding; chimeric Hsp110‑Hsp70 constructs can restore Hsp70‑like movements but impair NEF activity, and Sse1’s substrate‑binding specificity is governed mainly by its NBD rather than its SBD, which also chaperones itself and foreign NBDs.

Abstract

<h3>Abstract</h3> Hsp110s are well recognized nucleotide exchange factors (NEFs) of Hsp70s, in addition they are implicated in various aspects of cellular proteostasis as discrete chaperones with yet enigmatic molecular mechanism. Stark similarity in domain organization and structure between Hsp110s and Hsp70s, is easily discernible although the nature of domain communication and domain functions of Hsp110s are still puzzling. Here, we report atypical domain communication of yeast Hsp110, Sse1 using single molecule FRET, small angle X-ray scattering measurements (SAXS) and Molecular Dynamic simulations. Our data show that Sse1 lacks typical domain movements as exhibited by Hsp70s, albeit it undergoes unique structural alteration upon nucleotide and substrate binding. Hsp70-like domain-movements can be artificially salvaged in chimeric constructs of Hsp110-Hsp70 although such salvaging proves detrimental for the NEF activity of the protein. Furthermore, we show that substrate binding domain (SBD) of Hsp110, chaperones self, as well as foreign nucleotide binding domains (NBD). Interestingly, the substrate binding specificity of Hsp110 is largely determined by its NBD rather than SBD, the latter being the foremost substrate binding region for Hsp70s.