3qml | pdb_00003qml
The structural analysis of Sil1-Bip complex reveals the mechanism for Sil1 to function as a novel nucleotide exchange factor
Structural highlights
Function[GRP78_YEAST] Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER. Is required for secretory polypeptide translocation. May physically associate with SEC63 protein in the endoplasmic reticulum and this interaction may be regulated by ATP hydrolysis.[1] [SIL1_YEAST] Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone KAR2.[2] [3] [4] Publication Abstract from PubMedSil1 functions as a nucleotide exchange factor (NEF) for Bip in eukaryotic cells. In order to understand how Sil1 functions as a NEF, we analyzed the crystal structure of the yeast Bip-Sil1 complex at a resolution of 2.3A. In the complex, the Sil1 molecule acts as a "molecular clamp" which binds to the IIb lobe of the Bip ATPase domain. Sil1 binding causes lobe IIb to rotate ~13.5 degrees away from the ADP-binding pocket and lobe Ib to rotate in the opposite direction for ~3.7 degrees . These conformational changes in Bip open up the nucleotide-binding pocket in the ATPase domain and simultaneously disrupt the hydrogen bonds between Bip and bound ADP, thus providing a mechanism for ADP release. We also demonstrate that Sil1 mutations that disrupt binding to the Bip ATPase domain abolish Sil1's ability to stimulate Bip ATPase activity. Structural analysis of the Sil1-Bip complex reveals how Sil1 functions as a nucleotide exchange factor.,Yan M, Li J, Sha B Biochem J. 2011 Jun 15. PMID:21675960[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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