5kbx
From Proteopedia
Co-crystal structure of the Saccharomyces cerevisiae histidine phosphotransfer signaling protein Ypd1 and the receiver domain of its downstream response regulator Ssk1
Structural highlights
Function[YPD1_YEAST] Phosphorelay intermediate protein that is part of the branched SLN1-YPD1-SKN7/SSK1 two-component regulatory system, which controls activity of the HOG1 pathway and gene expression in response to changes in the osmolarity of the extracellular environment. Catalyzes the phosphoryl group transfer from the membrane-bound osmosensing histidine kinase SLN1 to two distinct response regulator proteins, SSK1 in the cytoplasm, and transcription factor SKN7 in the nucleus.[1] [2] [SSK1_YEAST] Final receptor of the SLN1-YPD1-SSK1 two-component regulatory system, which controls activity of the HOG1 pathway in response to changes in the osmolarity of the extracellular environment. Under normal osmotic conditions, maintained in a phosphorylated and inactive state by the phosphorelay intermediate protein YPD1. Under conditions of high osmolarity, the histidine kinase SLN1 is no longer active and the unphosphorylated form of SSK1 interacts with and activates SSK2 and SSK22, two MAPKKKs that further stimulate the PBS2-HOG1 MAPKK-MAPK cascade. Unphosphorylated SSK1 is subsequently degraded by the UBC7-dependent ubiquitin-proteasome system to down-regulate the HOG1 pathway after completion of the osmotic adaptation.[3] [4] [5] Publication Abstract from PubMedThe crystal structure of the yeast SLN1 response regulator (RR) domain bound to both a phosphoryl analog [beryllium fluoride (BeF(3)(-))] and Mg(2+), in complex with its downstream phosphorelay signaling partner YPD1, has been determined at a resolution of 1.70 A. Comparisons between the BeF(3)(-)-activated complex and the unliganded (or apo) complex determined previously reveal modest but important differences. The SLN1-R1 x Mg(2+) x BeF(3)(-) structure from the complex provides evidence for the first time that the mechanism of phosphorylation-induced activation is highly conserved between bacterial RR domains and this example from a eukaryotic organism. Residues in and around the active site undergo slight rearrangements in order to form bonds with the essential divalent cation and fluorine atoms of BeF(3)(-). Two conserved switch-like residues (Thr1173 and Phe1192) occupy distinctly different positions in the apo versus BeF(3)(-)-bound structures, consistent with the "Y-T" coupling mechanism proposed for the activation of CheY and other bacterial RRs. Several loop regions and the alpha 4-beta 5-alpha 5 surface of the SLN1-R1 domain undergo subtle conformational changes ( approximately 1-3 A displacements relative to the apo structure) that lead to significant changes in terms of contacts that are formed with YPD1. Detailed structural comparisons of protein-protein interactions in the apo and BeF(3)(-)-bound complexes suggest at least a two-state equilibrium model for the formation of a transient encounter complex, in which phosphorylation of the RR promotes the formation of a phosphotransfer-competent complex. In the BeF(3)(-)-activated complex, the position of His64 from YPD1 needs to be within ideal distance of and in near-linear geometry with Asp1144 from the SLN1-R1 domain for phosphotransfer to occur. The ground-state structure presented here suggests that phosphoryl transfer will likely proceed through an associative mechanism involving the formation of a pentacoordinate phosphorus intermediate. Crystal structure of a complex between the phosphorelay protein YPD1 and the response regulator domain of SLN1 bound to a phosphoryl analog.,Zhao X, Copeland DM, Soares AS, West AH J Mol Biol. 2008 Jan 25;375(4):1141-51. Epub 2007 Nov 22. PMID:18076904[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||
