The yeast YPD1/SLN1 complex: insights into molecular recognition in two-component signaling systems.

In Saccharomyces cerevisiae, a branched multistep phosphorelay signaling pathway regulates cellular adaptation to hyperosmotic stress. YPD1 functions as a histidine-phosphorylated protein intermediate required for phosphoryl group transfer from a membrane-bound sensor histidine kinase (SLN1) to two distinct response regulator proteins (SSK1 and SKN7). These four proteins are evolutionarily related to the well-characterized "two-component" regulatory proteins from bacteria. Although structural information is available for many two-component signaling proteins, there are very few examples of complexes between interacting phosphorelay partners. Here we report the first crystal structure of a prototypical monomeric histidine-containing phosphotransfer (HPt) protein YPD1 in complex with its upstream phosphodonor, the response regulator domain associated with SLN1.

[1]  Takeshi Mizuno,et al.  Insights into Multistep Phosphorelay from the Crystal Structure of the C-Terminal HPt Domain of ArcB , 1997, Cell.

[2]  M. Welch,et al.  Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY , 1998, Nature Structural Biology.

[3]  A. West,et al.  Conservation of structure and function among histidine-containing phosphotransfer (HPt) domains as revealed by the crystal structure of YPD1. , 1999, Journal of molecular biology.

[4]  J M Thornton,et al.  LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. , 1995, Protein engineering.

[5]  Ann M Stock,et al.  Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Jae Young Lee,et al.  Crystal structure and functional analysis of the SurE protein identify a novel phosphatase family , 2001, Nature Structural Biology.

[7]  F. Dahlquist,et al.  Phosphotransfer site of the chemotaxis-specific protein kinase CheA as revealed by NMR. , 1997, Biochemistry.

[8]  J. Pflugrath,et al.  The finer things in X-ray diffraction data collection. , 1999, Acta crystallographica. Section D, Biological crystallography.

[9]  D. Kahn,et al.  Conformational changes induced by phosphorylation of the FixJ receiver domain. , 1999, Structure.

[10]  J. L. Brown,et al.  Yeast Skn7p activity is modulated by the Sln1p-Ypd1p osmosensor and contributes to regulation of the HOG pathway , 1998, Molecular and General Genetics MGG.

[11]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[12]  Brian F. Volkman,et al.  Structure of a transiently phosphorylated switch in bacterial signal transduction , 2000, Nature.

[13]  S. Jones,et al.  Protein domain interfaces: characterization and comparison with oligomeric protein interfaces. , 2000, Protein engineering.

[14]  F. Dahlquist,et al.  The 1.9 A resolution crystal structure of phosphono-CheY, an analogue of the active form of the response regulator, CheY. , 2000, Biochemistry.

[15]  J. Thornton,et al.  Structural characterisation and functional significance of transient protein-protein interactions. , 2003, Journal of molecular biology.

[16]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[17]  E A Merritt,et al.  Raster3D: photorealistic molecular graphics. , 1997, Methods in enzymology.

[18]  A. West,et al.  Co-crystallization of the yeast phosphorelay protein YPD1 with the SLN1 response-regulator domain and preliminary X-ray diffraction analysis. , 2003, Acta crystallographica. Section D, Biological crystallography.

[19]  Rui Zhao,et al.  Structure and catalytic mechanism of the E . coli chemotaxis phosphatase CheZ , 2002 .

[20]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[21]  Yan Zhu,et al.  Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ , 1999, Nature Structural Biology.

[22]  J. Stock,et al.  Crystal Structure of the CheA Histidine Phosphotransfer Domain that Mediates Response Regulator Phosphorylation in Bacterial Chemotaxis* , 2001, The Journal of Biological Chemistry.

[23]  G. Murshudov,et al.  Refinement of macromolecular structures by the maximum-likelihood method. , 1997, Acta crystallographica. Section D, Biological crystallography.

[24]  R C Stewart,et al.  Yeast Skn7p functions in a eukaryotic two‐component regulatory pathway. , 1994, The EMBO journal.

[25]  A. Wilkinson,et al.  Phosphorylated aspartate in the structure of a response regulator protein. , 1999, Journal of molecular biology.

[26]  S J Remington,et al.  Two binding modes reveal flexibility in kinase/response regulator interactions in the bacterial chemotaxis pathway. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Michael Gurfinkel,et al.  Differential Stabilities of Phosphorylated Response Regulator Domains Reflect Functional Roles of the Yeast Osmoregulatory SLN1 and SSK1 Proteins , 1999, Journal of bacteriology.

[28]  Seok-Yong Lee,et al.  Crystal structure of an activated response regulator bound to its target , 2001, Nature Structural Biology.

[29]  Francesc Posas,et al.  Yeast HOG1 MAP Kinase Cascade Is Regulated by a Multistep Phosphorelay Mechanism in the SLN1–YPD1–SSK1 “Two-Component” Osmosensor , 1996, Cell.

[30]  P. Matsumura,et al.  Crystal structure of Escherichia coli CheY refined at 1.7-A resolution. , 1993, The Journal of biological chemistry.

[31]  S. Kim,et al.  The structure of the signal receiver domain of the Arabidopsis thaliana ethylene receptor ETR1. , 1999, Structure.

[32]  Ann M Stock,et al.  Histidine kinases and response regulator proteins in two-component signaling systems. , 2001, Trends in biochemical sciences.

[33]  M G Lee,et al.  Insights into eukaryotic multistep phosphorelay signal transduction revealed by the crystal structure of Ypd1p from Saccharomyces cerevisiae. , 1999, Journal of molecular biology.

[34]  D. McRee.  Practical Protein Crystallography , 1993 .

[35]  K. Shinozaki,et al.  Two-component systems in plant signal transduction. , 2000, Trends in plant science.

[36]  R. Laskowski.  SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. , 1995, Journal of molecular graphics.

[37]  J. Hoch,et al.  A transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in signal transduction. , 2000, Structure.

[38]  D E Wemmer,et al.  Three-dimensional solution structure of the N-terminal receiver domain of NTRC. , 1995, Biochemistry.

[39]  A. West,et al.  Novel Role for an HPt Domain in Stabilizing the Phosphorylated State of a Response Regulator Domain , 2000, Journal of bacteriology.

[40]  Sheng Li,et al.  The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p , 1998, The EMBO journal.

[41]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[42]  A. Vagin,et al.  MOLREP: an Automated Program for Molecular Replacement , 1997 .

[43]  G. Petsko,et al.  Structure of the Mg(2+)-bound form of CheY and mechanism of phosphoryl transfer in bacterial chemotaxis. , 1994, Biochemistry.

[44]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[45]  R. Dickerson,et al.  Structure of the Escherichia coli response regulator NarL. , 1996, Biochemistry.

[46]  J. Thornton,et al.  PROMOTIF—A program to identify and analyze structural motifs in proteins , 1996, Protein science : a publication of the Protein Society.

[47]  N. Xuong,et al.  Crystal structure of a phosphatase-resistant mutant of sporulation response regulator Spo0F from Bacillus subtilis. , 1996, Structure.

[48]  J. Hoch,et al.  Keeping Signals Straight in Phosphorelay Signal Transduction , 2001, Journal of bacteriology.

[49]  A. West,et al.  Ssk1p Response Regulator Binding Surface on Histidine- Containing Phosphotransfer Protein Ypd1p , 2003, Eukaryotic Cell.

[50]  Ann M Stock,et al.  Two-component signal transduction. , 2000, Annual review of biochemistry.

[51]  J. Hoch,et al.  Formation of a novel four-helix bundle and molecular recognition sites by dimerization of a response regulator phosphotransferase. , 1998, Molecular cell.

[52]  Ann M Stock,et al.  A tale of two components: a novel kinase and a regulatory switch , 2000, Nature Structural Biology.

[53]  J. S. Parkinson,et al.  NMR structure of activated CheY. , 2000, Journal of molecular biology.

[54]  B. Matthews.  Solvent content of protein crystals. , 1968, Journal of molecular biology.