The crystal structure of the Sgt1-Skp1 complex: the link between Hsp90 and both SCF E3 ubiquitin ligases and kinetochores.

摘要: The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways interacts with Skp1, small protein that heterodimerizes proteins containing F-box motif. We have determined crystal structure interacting domains Saccharomyces cerevisiae Skp1 at 2.8 A resolution validated interface context full-length solution. BTB/POZ domain associates via concave surface its TPR using residues are conserved humans. Dimerization yeast occurs an insertion is absent from monomeric human Sgt1. identify point mutations disrupt dimerization binding vitro find interaction function yeast. Our data provide structural rationale for understanding phenotypes temperature-sensitive mutants linking Skp1-associated Hsp90-dependent pathways.