2v3s: Difference between revisions

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[[Image:2v3s.gif|left|200px]]


{{Structure
==Structural insights into the recognition of substrates and activators by the OSR1 kinase==
|PDB= 2v3s |SIZE=350|CAPTION= <scene name='initialview01'>2v3s</scene>, resolution 1.70&Aring;
<StructureSection load='2v3s' size='340' side='right'caption='[[2v3s]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Act+Binding+Site+For+Chain+B'>AC1</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=ACT:ACETATE ION'>ACT</scene>
<table><tr><td colspan='2'>[[2v3s]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V3S FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2v3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v3s OCA], [https://pdbe.org/2v3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v3s RCSB], [https://www.ebi.ac.uk/pdbsum/2v3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v3s ProSAT]</span></td></tr>
 
</table>
'''STRUCTURAL INSIGHTS INTO THE RECOGNITION OF SUBSTRATES AND ACTIVATORS BY THE OSR1 KINASE'''
== Function ==
 
[https://www.uniprot.org/uniprot/OXSR1_HUMAN OXSR1_HUMAN] Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton.<ref>PMID:14707132</ref>
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v3/2v3s_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v3s ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signalling cascade regulating the activity of Na(+)/K(+)/2Cl(-) co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as its substrates (NKCC1 and NKCC2). Here, we describe the structural basis of this recognition event as shown by the crystal structure of the CCT domain of OSR1 in complex with a peptide containing this motif, derived from WNK4. The CCT domain forms a novel protein fold that interacts with the Arg-Phe-Xaa-Val motif through a surface-exposed groove. An intricate web of interactions is observed between the CCT domain and an Arg-Phe-Xaa-Val motif-containing peptide derived from WNK4. Mutational analysis shows that these interactions are required for the CCT domain to bind to WNK1 and NKCC1. The CCT domain structure also shows how phosphorylation of a Ser/Thr residue preceding the Arg-Phe-Xaa-Val motif results in a steric clash, promoting its dissociation from the CCT domain. These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates.
The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signalling cascade regulating the activity of Na(+)/K(+)/2Cl(-) co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as its substrates (NKCC1 and NKCC2). Here, we describe the structural basis of this recognition event as shown by the crystal structure of the CCT domain of OSR1 in complex with a peptide containing this motif, derived from WNK4. The CCT domain forms a novel protein fold that interacts with the Arg-Phe-Xaa-Val motif through a surface-exposed groove. An intricate web of interactions is observed between the CCT domain and an Arg-Phe-Xaa-Val motif-containing peptide derived from WNK4. Mutational analysis shows that these interactions are required for the CCT domain to bind to WNK1 and NKCC1. The CCT domain structure also shows how phosphorylation of a Ser/Thr residue preceding the Arg-Phe-Xaa-Val motif results in a steric clash, promoting its dissociation from the CCT domain. These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates.


==Disease==
Structural insights into the recognition of substrates and activators by the OSR1 kinase.,Villa F, Goebel J, Rafiqi FH, Deak M, Thastrup J, Alessi DR, van Aalten DM EMBO Rep. 2007 Sep;8(9):839-45. Epub 2007 Aug 17. PMID:17721439<ref>PMID:17721439</ref>
Known diseases associated with this structure: Pseudohypoaldosteronism type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601844 601844]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2V3S is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V3S OCA].
</div>
<div class="pdbe-citations 2v3s" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural insights into the recognition of substrates and activators by the OSR1 kinase., Villa F, Goebel J, Rafiqi FH, Deak M, Thastrup J, Alessi DR, van Aalten DM, EMBO Rep. 2007 Sep;8(9):839-45. Epub 2007 Aug 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17721439 17721439]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Alessi DR]]
[[Category: Aalten, D M.F Van.]]
[[Category: Deak M]]
[[Category: Alessi, D R.]]
[[Category: Goebel J]]
[[Category: Deak, M.]]
[[Category: Rafiqi FH]]
[[Category: Goebel, J.]]
[[Category: Thastrup J]]
[[Category: Rafiqi, F H.]]
[[Category: Villa F]]
[[Category: Thastrup, J.]]
[[Category: Van Aalten DMF]]
[[Category: Villa, F.]]
[[Category: ACT]]
[[Category: atp-binding]]
[[Category: kinase]]
[[Category: magnesium]]
[[Category: metal-binding]]
[[Category: nucleotide-binding]]
[[Category: phosphorylation]]
[[Category: polymorphism]]
[[Category: serine/threonine-protein kinase]]
[[Category: transferase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:42:58 2008''

Latest revision as of 12:54, 9 May 2024

Structural insights into the recognition of substrates and activators by the OSR1 kinaseStructural insights into the recognition of substrates and activators by the OSR1 kinase

Structural highlights

2v3s is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OXSR1_HUMAN Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signalling cascade regulating the activity of Na(+)/K(+)/2Cl(-) co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as its substrates (NKCC1 and NKCC2). Here, we describe the structural basis of this recognition event as shown by the crystal structure of the CCT domain of OSR1 in complex with a peptide containing this motif, derived from WNK4. The CCT domain forms a novel protein fold that interacts with the Arg-Phe-Xaa-Val motif through a surface-exposed groove. An intricate web of interactions is observed between the CCT domain and an Arg-Phe-Xaa-Val motif-containing peptide derived from WNK4. Mutational analysis shows that these interactions are required for the CCT domain to bind to WNK1 and NKCC1. The CCT domain structure also shows how phosphorylation of a Ser/Thr residue preceding the Arg-Phe-Xaa-Val motif results in a steric clash, promoting its dissociation from the CCT domain. These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates.

Structural insights into the recognition of substrates and activators by the OSR1 kinase.,Villa F, Goebel J, Rafiqi FH, Deak M, Thastrup J, Alessi DR, van Aalten DM EMBO Rep. 2007 Sep;8(9):839-45. Epub 2007 Aug 17. PMID:17721439[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Chen W, Yazicioglu M, Cobb MH. Characterization of OSR1, a member of the mammalian Ste20p/germinal center kinase subfamily. J Biol Chem. 2004 Mar 19;279(12):11129-36. Epub 2004 Jan 5. PMID:14707132 doi:10.1074/jbc.M313562200
  2. ↑ Villa F, Goebel J, Rafiqi FH, Deak M, Thastrup J, Alessi DR, van Aalten DM. Structural insights into the recognition of substrates and activators by the OSR1 kinase. EMBO Rep. 2007 Sep;8(9):839-45. Epub 2007 Aug 17. PMID:17721439

2v3s, resolution 1.70Å

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