Insights revealed by the co-crystal structure of the Saccharomyces cerevisiae histidine phosphotransfer protein Ypd1 and the receiver domain of its downstream response regulator Ssk1

Branscum, Katie M.; Menon, Smita K.; Foster, Clay A.; West, Ann H.

doi:10.1002/pro.3755

Title: Insights revealed by the co-crystal structure of the Saccharomyces cerevisiae histidine phosphotransfer protein Ypd1 and the receiver domain of its downstream response regulator Ssk1

Journal Article · Mon Oct 21 00:00:00 EDT 2019 · Protein Science

DOI:https://doi.org/10.1002/pro.3755· OSTI ID:1623588

Branscum, Katie M. ^[1]; Menon, Smita K. ^[1]; Foster, Clay A. ^[2];

^[1]

Univ. of Oklahoma, Norman, OK (United States). Dept. of Chemistry and Biochemistry
Univ. of Oklahoma, Norman, OK (United States). Dept. of Chemistry and Biochemistry; Univ. of North Carolina, Chapel Hill, NC (United States). Dept.of Microbiology and Immunology

Two-component signaling systems are the primary means by which bacteria, archaea, and certain plants and fungi react to their environments. The model yeast, Saccharomyces cerevisiae, uses the Sln1 signaling pathway to respond to hyperosmotic stress. This pathway contains a hybrid histidine kinase (Sln1) that autophosphorylates and transfers a phosphoryl group to its own receiver domain (R1). The phosphoryl group is then transferred to a histidine phosphotransfer protein (Ypd1) that finally passes it to the receiver domain (R2) of a downstream response regulator (Ssk1). Under normal conditions, Ssk1 is constitutively and preferentially phosphorylated in the phosphorelay. Upon detecting hyperosmotic stress, Ssk1 rapidly dephosphorylates and activates the high-osmolarity glycerol (HOG) pathway, initiating a response. Despite their distinct physiological roles, both Sln1 and Ssk1 bind to Ypd1 at a common docking site. Co-crystal structures of response regulators in complex with their phosphorelay partners are scarce, leaving many mechanistic and structural details uncharacterized for systems like the Sln1 pathway. In this work, we present the co-crystal structure of Ypd1 and a near wild-type variant of the receiver domain of Ssk1 (Ssk1-R2-W638A) at a resolution of 2.80 Å. Our structural analyses of Ypd1-receiver domain complexes, biochemical determination of binding affinities for Ssk1-R2 variants, in silico free energy estimates, and sequence comparisons reveal distinctive electrostatic properties of the Ypd1/ Ssk1-R2-W638A complex that may provide insight into the regulation of the Sln1 pathway as a function of dynamic osmolyte concentration.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1623588

Journal Information:: Protein Science, Vol. 28, Issue 12; ISSN 0961-8368

Publisher:: The Protein SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (67)

Principles of protein-protein interactions. Jones, S.; Thornton, J. M. Proceedings of the National Academy of Sciences, Vol. 93, Issue 1 https://doi.org/10.1073/pnas.93.1.13	journal	January 1996
Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of p K _a Values Søndergaard, Chresten R.; Olsson, Mats H. M.; Rostkowski, Michał Journal of Chemical Theory and Computation, Vol. 7, Issue 7 https://doi.org/10.1021/ct200133y	journal	June 2011
CHARMM: the biomolecular simulation program Brooks, B. R.; Brooks, C. L.; Mackerell, A. D. Wiley-Blackwell https://doi.org/10.5167/uzh-19245	text	January 2009
MMPBSA.py : An Efficient Program for End-State Free Energy Calculations Miller, Bill R.; McGee, T. Dwight; Swails, Jason M. Journal of Chemical Theory and Computation, Vol. 8, Issue 9 https://doi.org/10.1021/ct300418h	journal	August 2012
UniProt: the universal protein knowledgebase Nucleic Acids Research, Vol. 45, Issue D1, p. D158-D169 https://doi.org/10.1093/nar/gkw1099	journal	November 2016
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
Insights into Protein–Protein Binding by Binding Free Energy Calculation and Free Energy Decomposition for the Ras–Raf and Ras–RalGDS Complexes Gohlke, Holger; Kiel, Christina; Case, David A. Journal of Molecular Biology, Vol. 330, Issue 4 https://doi.org/10.1016/S0022-2836(03)00610-7	journal	July 2003
Representative Proteomes: A Stable, Scalable and Unbiased Proteome Set for Sequence Analysis and Functional Annotation Chen, Chuming; Natale, Darren A.; Finn, Robert D. PLoS ONE, Vol. 6, Issue 4 https://doi.org/10.1371/journal.pone.0018910	journal	April 2011
Effects of Osmolytes on the SLN1-YPD1-SSK1 Phosphorelay System from Saccharomyces cerevisiae Kaserer, Alla O.; Andi, Babak; Cook, Paul F. Biochemistry, Vol. 48, Issue 33 https://doi.org/10.1021/bi900886g	journal	August 2009
Differential Stabilities of Phosphorylated Response Regulator Domains Reflect Functional Roles of the Yeast Osmoregulatory SLN1 and SSK1 Proteins Janiak-Spens, Fabiola; Sparling, Jeffrey M.; Gurfinkel, Michael Journal of Bacteriology, Vol. 181, Issue 2 https://doi.org/10.1128/JB.181.2.411-417.1999	journal	January 1999
Scalable molecular dynamics with NAMD Phillips, James C.; Braun, Rosemary; Wang, Wei Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802 https://doi.org/10.1002/jcc.20289	journal	January 2005
The Activation of RalGDS Can Be Achieved Independently of Its Ras Binding Domain: IMPLICATIONS OF AN ACTIVATION MECHANISM IN Ras EFFECTOR SPECIFICITY AND SIGNAL DISTRIBUTION Linnemann, Thomas; Kiel, Christina; Herter, Peter Journal of Biological Chemistry, Vol. 277, Issue 10 https://doi.org/10.1074/jbc.M110800200	journal	December 2001
Improved Generalized Born Solvent Model Parameters for Protein Simulations Nguyen, Hai; Roe, Daniel R.; Simmerling, Carlos Journal of Chemical Theory and Computation, Vol. 9, Issue 4 https://doi.org/10.1021/ct3010485	journal	March 2013
Generalized Born Model with a Simple, Robust Molecular Volume Correction Mongan, John; Simmerling, Carlos; McCammon, J. Andrew Journal of Chemical Theory and Computation, Vol. 3, Issue 1 https://doi.org/10.1021/ct600085e	journal	December 2006
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
Composition Profiler: a tool for discovery and visualization of amino acid composition differences Vacic, Vladimir; Uversky, Vladimir N.; Dunker, A. Keith BMC Bioinformatics, Vol. 8, Issue 1 https://doi.org/10.1186/1471-2105-8-211	journal	January 2007
Two-Component Systems and Their Co-Option for Eukaryotic Signal Transduction Schaller, G. Eric; Shiu, Shin-Han; Armitage, Judith P. Current Biology, Vol. 21, Issue 9 https://doi.org/10.1016/j.cub.2011.02.045	journal	May 2011
Exploring protein native states and large-scale conformational changes with a modified generalized born model Onufriev, Alexey; Bashford, Donald; Case, David A. Proteins: Structure, Function, and Bioinformatics, Vol. 55, Issue 2 https://doi.org/10.1002/prot.20033	journal	March 2004
A common docking site for response regulators on the yeast phosphorelay protein YPD1 Porter, Stace W.; West, Ann H. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1748, Issue 2 https://doi.org/10.1016/j.bbapap.2004.12.009	journal	May 2005
Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin Van Duyne, Gregory D.; Standaert, Robert F.; Karplus, P. Andrew Journal of Molecular Biology, Vol. 229, Issue 1 https://doi.org/10.1006/jmbi.1993.1012	journal	January 1993
Two-Component Signal Transduction Stock, Ann M.; Robinson, Victoria L.; Goudreau, Paul N. Annual Review of Biochemistry, Vol. 69, Issue 1 https://doi.org/10.1146/annurev.biochem.69.1.183	journal	June 2000
Two-component signal transduction Bourret, Robert B.; Silversmith, Ruth E. Current Opinion in Microbiology, Vol. 13, Issue 2 https://doi.org/10.1016/j.mib.2010.02.003	journal	April 2010
CHARMM: The biomolecular simulation program Brooks, B. R.; Brooks, C. L.; Mackerell, A. D. Journal of Computational Chemistry, Vol. 30, Issue 10 https://doi.org/10.1002/jcc.21287	journal	July 2009
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability Katoh, K.; Standley, D. M. Molecular Biology and Evolution, Vol. 30, Issue 4 https://doi.org/10.1093/molbev/mst010	journal	January 2013
Parametrized Models of Aqueous Free Energies of Solvation Based on Pairwise Descreening of Solute Atomic Charges from a Dielectric Medium Hawkins, Gregory D.; Cramer, Christopher J.; Truhlar, Donald G. The Journal of Physical Chemistry, Vol. 100, Issue 51 https://doi.org/10.1021/jp961710n	journal	January 1996
WebLogo: A Sequence Logo Generator Crooks, Gavin E.; Hon, Gary; Chandonia, John-Marc Genome Research, Vol. 14, Issue 6, p. 1188-1190 https://doi.org/10.1101/gr.849004	journal	May 2004
UniProt: the universal protein knowledgebase UniProt Consortium, The Nucleic Acids Research, Vol. 46, Issue 5 https://doi.org/10.1093/nar/gky092	journal	February 2018
Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis Strong, M.; Sawaya, M. R.; Wang, S. Proceedings of the National Academy of Sciences, Vol. 103, Issue 21 https://doi.org/10.1073/pnas.0602606103	journal	May 2006
PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical p K _a Predictions Olsson, Mats H. M.; Søndergaard, Chresten R.; Rostkowski, Michal Journal of Chemical Theory and Computation, Vol. 7, Issue 2 https://doi.org/10.1021/ct100578z	journal	December 2010
The Pfam protein families database in 2019 El-Gebali, Sara; Mistry, Jaina; Bateman, Alex Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky995	journal	October 2018
Response to Hyperosmotic Stress Saito, Haruo; Posas, Francesc Genetics, Vol. 192, Issue 2 https://doi.org/10.1534/genetics.112.140863	journal	October 2012
Purification, crystallization and preliminary X-ray diffraction analysis of the yeast phosphorelay protein YPD1 Xu, Qingping; Nguyen, Viet; West, Ann H. Acta Crystallographica Section D Biological Crystallography, Vol. 55, Issue 1 https://doi.org/10.1107/S090744499800866X	journal	January 1999
The Yeast YPD1/SLN1 Complex Xu, Qingping; Porter, Stace W.; West, Ann H. Structure, Vol. 11, Issue 12 https://doi.org/10.1016/j.str.2003.10.016	journal	December 2003
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
UniProt: the Universal Protein knowledgebase Apweiler, R. Nucleic Acids Research, Vol. 32, Issue 90001 https://doi.org/10.1093/nar/gkh131	journal	January 2004
Transient Kinetic Studies on the Interaction of Ras and the Ras-Binding Domain of c-Raf-1 Reveal Rapid Equilibration of the Complex ^† Sydor, Jens R.; Engelhard, Martin; Wittinghofer, Alfred Biochemistry, Vol. 37, Issue 40 https://doi.org/10.1021/bi980764f	journal	October 1998
PROMALS3D: a tool for multiple protein sequence and structure alignments Pei, Jimin; Kim, Bong-Hyun; Grishin, Nick V. Nucleic Acids Research, Vol. 36, Issue 7 https://doi.org/10.1093/nar/gkn072	journal	February 2008
Role of the highly conserved G68 residue in the yeast phosphorelay protein Ypd1: implications for interactions between histidine phosphotransfer (HPt) and response regulator proteins N., Kennedy, Emily; A., Foster, Clay; K., Menon, Smita BioMed Central https://doi.org/10.17615/7khw-5065	text	January 2019
Role of the highly conserved G68 residue in the yeast phosphorelay protein Ypd1: implications for interactions between histidine phosphotransfer (HPt) and response regulator proteins Kennedy, Emily N.; Hebdon, Skyler D.; Menon, Smita K. BMC Biochemistry, Vol. 20, Issue 1 https://doi.org/10.1186/s12858-019-0104-5	journal	January 2019
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Electrostatically optimized Ras-binding Ral guanine dissociation stimulator mutants increase the rate of association by stabilizing the encounter complex Kiel, C.; Selzer, T.; Shaul, Y. Proceedings of the National Academy of Sciences, Vol. 101, Issue 25 https://doi.org/10.1073/pnas.0401160101	journal	June 2004
Electrostatic aspects of protein–protein interactions Sheinerman, F. Current Opinion in Structural Biology, Vol. 10, Issue 2 https://doi.org/10.1016/S0959-440X(00)00065-8	journal	April 2000
On the treatment of negative intensity observations French, S.; Wilson, K. Acta Crystallographica Section A, Vol. 34, Issue 4 https://doi.org/10.1107/S0567739478001114	journal	July 1978
Two-Component Sensing and Regulation: How Do Histidine Kinases Talk with Response Regulators at the Molecular Level? Buschiazzo, Alejandro; Trajtenberg, Felipe Annual Review of Microbiology, Vol. 73, Issue 1 https://doi.org/10.1146/annurev-micro-091018-054627	journal	September 2019
Protein–Protein Interactions: Hot Spots and Structurally Conserved Residues often Locate in Complemented Pockets that Pre-organized in the Unbound States: Implications for Docking Li, Xiang; Keskin, Ozlem; Ma, Buyong Journal of Molecular Biology, Vol. 344, Issue 3 https://doi.org/10.1016/j.jmb.2004.09.051	journal	November 2004
Improvements to the APBS biomolecular solvation software suite: Improvements to the APBS Software Suite Jurrus, Elizabeth; Engel, Dave; Star, Keith Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3280	journal	October 2017
Overview of the CCP4 suite and current developments. Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.52322	text	January 2011
Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins Carim, Sean; Azadeh, Ashley L.; Kazakov, Alexey E. The ISME Journal, Vol. 15, Issue 8 https://doi.org/10.1038/s41396-021-00921-1	journal	March 2021
Crystal Structure of a Complex between the Phosphorelay Protein YPD1 and the Response Regulator Domain of SLN1 Bound to a Phosphoryl Analog Zhao, Xiaodong; Copeland, Daniel M.; Soares, Alexei S. Journal of Molecular Biology, Vol. 375, Issue 4 https://doi.org/10.1016/j.jmb.2007.11.045	journal	January 2008
HMMER web server: interactive sequence similarity searching Finn, R. D.; Clements, J.; Eddy, S. R. Nucleic Acids Research, Vol. 39, Issue suppl https://doi.org/10.1093/nar/gkr367	journal	May 2011
On the role of electrostatics in protein–protein interactions Zhang, Zhe; Witham, Shawn; Alexov, Emil Physical Biology, Vol. 8, Issue 3 https://doi.org/10.1088/1478-3975/8/3/035001	journal	May 2011
Functional roles of conserved amino acid residues surrounding the phosphorylatable histidine of the yeast phosphorelay protein YPD1 Janiak-Spens, Fabiola; West, Ann H. Molecular Microbiology, Vol. 37, Issue 1 https://doi.org/10.1046/j.1365-2958.2000.01973.x	journal	July 2000
Protein-protein interactions: General trends in the relationship between binding affinity and interfacial buried surface area: Protein-protein Interactions Chen, Jieming; Sawyer, Nicholas; Regan, Lynne Protein Science, Vol. 22, Issue 4 https://doi.org/10.1002/pro.2230	journal	February 2013
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Interaction Dynamics Determine Signaling and Output Pathway Responses Stojanovski, Klement; Ferrar, Tony; Benisty, Hannah Cell Reports, Vol. 19, Issue 1 https://doi.org/10.1016/j.celrep.2017.03.029	journal	April 2017
PDBsum: Structural summaries of PDB entries Laskowski, Roman A.; Jabłońska, Jagoda; Pravda, Lukáš Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3289	journal	October 2017
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Kinetic Analysis of YPD1-Dependent Phosphotransfer Reactions in the Yeast Osmoregulatory Phosphorelay System ^† Janiak-Spens, Fabiola; Cook, Paul F.; West, Ann H. Biochemistry, Vol. 44, Issue 1 https://doi.org/10.1021/bi048433s	journal	January 2005
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Improvements to the APBS biomolecular solvation software suite Jurrus, Elizabeth; Engel, Dave; Star, Keith arXiv https://doi.org/10.48550/arxiv.1707.00027	text	January 2017
Yeast HOG1 MAP Kinase Cascade Is Regulated by a Multistep Phosphorelay Mechanism in the SLN1–YPD1–SSK1 “Two-Component” Osmosensor Posas, Francesc; Wurgler-Murphy, Susannah M.; Maeda, Tatsuya Cell, Vol. 86, Issue 6 https://doi.org/10.1016/s0092-8674(00)80162-2	journal	September 1996
Histidine Phosphorylation and Two-Component Signaling in Eukaryotic Cells Saito, Haruo Chemical Reviews, Vol. 101, Issue 8 https://doi.org/10.1021/cr000243+	journal	July 2001
Histidine Phosphotransfer Proteins in Fungal Two-Component Signal Transduction Pathways Fassler, Jan S.; West, Ann H. Eukaryotic Cell, Vol. 12, Issue 8 https://doi.org/10.1128/ec.00083-13	journal	June 2013
Novel Role for an HPt Domain in Stabilizing the Phosphorylated State of a Response Regulator Domain Janiak-Spens, Fabiola; Sparling, David P.; West, Ann H. Journal of Bacteriology, Vol. 182, Issue 23 https://doi.org/10.1128/jb.182.23.6673-6678.2000	journal	December 2000
Phosphorylated Ssk1 Prevents Unphosphorylated Ssk1 from Activating the Ssk2 Mitogen-Activated Protein Kinase Kinase Kinase in the Yeast High-Osmolarity Glycerol Osmoregulatory Pathway Horie, Tetsuro; Tatebayashi, Kazuo; Yamada, Rika Molecular and Cellular Biology, Vol. 28, Issue 17 https://doi.org/10.1128/mcb.00589-08	journal	June 2008

Figures / Tables (7)

Similar Records

Crystal Structure of a Complex Between the Phosphorelay Protein YPD1 and the Response Regulator Domain of SLN1 Bound to a Phosphoryl Analog

Journal Article · Tue Jan 01 00:00:00 EST 2008 · Journal of Molecular Biology · OSTI ID:1623588

Zhao, X; Copeland, D; Soares, A; +1 more

Imidazole as a Small Molecule Analogue in Two-Component Signal Transduction

Journal Article · Wed Dec 02 00:00:00 EST 2015 · Biochemistry · OSTI ID:1623588

Page, Stephani C.; Silversmith, Ruth E.; Collins, Edward J.; +1 more

Role of the highly conserved G68 residue in the yeast phosphorelay protein Ypd1: implications for interactions between histidine phosphotransfer (HPt) and response regulator proteins

Journal Article · Mon Jan 21 00:00:00 EST 2019 · BMC Biochemistry (Online) · OSTI ID:1623588

Kennedy, Emily N.; Hebdon, Skyler D.; Menon, Smita K.; +5 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
two-component signaling
Ypd1
Ssk1
response regulator
histidine phosphotransfer protein
Saccharomyces cerevisiae
co-crystal
phosphotransfer

Title: Insights revealed by the co-crystal structure of the Saccharomyces cerevisiae histidine phosphotransfer protein Ypd1 and the receiver domain of its downstream response regulator Ssk1

Citation Formats

References (67)

Figures / Tables (7)

Similar Records

Related Subjects