2oj2: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)== | ==NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)== | ||
<StructureSection load='2oj2' size='340' side='right' caption='[[2oj2 | <StructureSection load='2oj2' size='340' side='right'caption='[[2oj2]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2oj2]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2oj2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2a4y 2a4y]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OJ2 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oj2 OCA], [https://pdbe.org/2oj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oj2 RCSB], [https://www.ebi.ac.uk/pdbsum/2oj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oj2 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oj/2oj2_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oj/2oj2_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=2oj2 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 30: | Line 30: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2oj2" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Tyrosine kinase|Tyrosine kinase]] | *[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 38: | Line 39: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Hoffmann | [[Category: Hoffmann S]] | ||
[[Category: Schmidt | [[Category: Schmidt H]] | ||
[[Category: Stangler | [[Category: Stangler T]] | ||
[[Category: Stoldt | [[Category: Stoldt M]] | ||
[[Category: Tran | [[Category: Tran T]] | ||
[[Category: Wiesehan | [[Category: Wiesehan K]] | ||
[[Category: Willbold | [[Category: Willbold D]] | ||
Latest revision as of 03:19, 28 December 2023
NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)
Structural highlights
DiseaseHCK_HUMAN Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.[1] [2] Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.[3] [4] FunctionHCK_HUMAN Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] 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 PubMedWe studied the interaction of hematopoietic cell kinase SH3 domain (HckSH3) with an artificial 12-residue proline-rich peptide PD1 (HSKYPLPPLPSL) identified as high affinity ligand (K(D)=0.2 muM). PD1 shows an unusual ligand sequence for SH3 binding in type I orientation because it lacks the typical basic anchor residue at position P(-3), but instead has a tyrosine residue at this position. A basic lysine residue, however, is present at position P(-4). The solution structure of the HckSH3:PD1 complex, which is the first HckSH3 complex structure available, clearly reveals that the P(-3) tyrosine residue of PD1 does not take the position of the typical anchor residue but rather forms additional van der Waals interactions with the HckSH3 RT loop. Instead, lysine at position P(-4) of PD1 substitutes the function of the P(-3) anchor residue. This finding expands the well known ligand consensus sequence +xxPpxP by +xxxPpxP. Thus, software tools like iSPOT fail to identify PD1 as a high-affinity HckSH3 ligand so far. In addition, a short antiparallel beta-sheet in the RT loop of HckSH3 is observed upon PD1 binding. The structure of the HckSH3:PD1 complex reveals novel features of SH3 ligand binding and yields new insights into the structural basics of SH3-ligand interactions. Consequences for computational prediction tools adressing SH3-ligand interactions as well as the biological relevance of our findings are discussed. Solution structure of a Hck SH3 domain ligand complex reveals novel interaction modes.,Schmidt H, Hoffmann S, Tran T, Stoldt M, Stangler T, Wiesehan K, Willbold D J Mol Biol. 2007 Feb 2;365(5):1517-32. Epub 2006 Nov 10. PMID:17141806[24] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||