6roz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:25, 23 October 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 3: Line 3:
<StructureSection load='6roz' size='340' side='right'caption='[[6roz]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
<StructureSection load='6roz' size='340' side='right'caption='[[6roz]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[6roz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ROZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ROZ FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6roz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ROZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ROZ FirstGlance]. <br>
-
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89&#8491;</td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6roz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6roz OCA], [http://pdbe.org/6roz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6roz RCSB], [http://www.ebi.ac.uk/pdbsum/6roz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6roz ProSAT]</span></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=6roz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6roz OCA], [https://pdbe.org/6roz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6roz RCSB], [https://www.ebi.ac.uk/pdbsum/6roz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6roz ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
-
[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[http://omim.org/entry/151100 151100]]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[http://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[http://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>
+
[https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:[https://omim.org/entry/605218 605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:12402038</ref>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>
+
[https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.<ref>PMID:21276005</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
In cancer, the programmed death-1 (PD-1) pathway suppresses T cell stimulation and mediates immune escape. Upon stimulation, PD-1 becomes phosphorylated at its immune receptor tyrosine-based inhibitory motif (ITIM) and immune receptor tyrosine-based switch motif (ITSM), which then bind the Src homology 2 (SH2) domains of SH2-containing phosphatase 2 (SHP2), initiating T cell inactivation. The SHP2-PD-1 complex structure and the exact functions of the two SH2 domains and phosphorylated motifs remain unknown. Here, we explain the structural basis and provide functional evidence for the mechanism of PD-1-mediated SHP2 activation. We demonstrate that full activation is obtained only upon phosphorylation of both ITIM and ITSM: ITSM binds C-SH2 with strong affinity, recruiting SHP2 to PD-1, while ITIM binds N-SH2, displacing it from the catalytic pocket and activating SHP2. This binding event requires the formation of a new inter-domain interface, offering opportunities for the development of novel immunotherapeutic approaches.
 +
 
 +
Molecular mechanism of SHP2 activation by PD-1 stimulation.,Marasco M, Berteotti A, Weyershaeuser J, Thorausch N, Sikorska J, Krausze J, Brandt HJ, Kirkpatrick J, Rios P, Schamel WW, Kohn M, Carlomagno T Sci Adv. 2020 Jan 31;6(5):eaay4458. doi: 10.1126/sciadv.aay4458. eCollection 2020, Jan. PMID:32064351<ref>PMID:32064351</ref>
 +
 
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 6roz" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Protein-tyrosine-phosphatase]]
+
[[Category: Synthetic construct]]
-
[[Category: Carlomagno, T]]
+
[[Category: Carlomagno T]]
-
[[Category: Krausze, J]]
+
[[Category: Krausze J]]
-
[[Category: Sikorska, J]]
+
[[Category: Sikorska J]]
-
[[Category: Cell cycle]]
+
-
[[Category: Immune receptor tyrosine-based switch motif]]
+
-
[[Category: Inhibitory peptide]]
+
-
[[Category: Itsm]]
+
-
[[Category: Phosphatase]]
+
-
[[Category: Signal transducer]]
+
-
[[Category: Src homology-2 domain]]
+

Current revision

Structure of the N-SH2 domain of the human tyrosine-protein phosphatase non-receptor type 11 in complex with the phosphorylated immune receptor tyrosine-based switch motif

PDB ID 6roz

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6roz"
Personal tools