Structural analysis of the Sil1-Bip complex reveals how Sil1 functions as a nucleotide exchange factor.
Sil1 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° away from the ADP-binding pocket and lobe Ib to rotate in the opposite direction for ~3.7°. 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.
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Date: Jun. 15, 2011
PubMed ID: 21675960
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