1d4t

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH A SLAM PEPTIDE

Structural highlights

1d4t is a 2 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 1.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SH21A_HUMAN Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) [MIM:308240; also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Function

SH21A_HUMAN Inhibitor of the SLAM self-association. Acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. Mediates interaction between FYN and SLAMF1. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.

Evolutionary Conservation

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

References

↑ Morra M, Simarro-Grande M, Martin M, Chen AS, Lanyi A, Silander O, Calpe S, Davis J, Pawson T, Eck MJ, Sumegi J, Engel P, Li SC, Terhorst C. Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients. J Biol Chem. 2001 Sep 28;276(39):36809-16. Epub 2001 Jul 26. PMID:11477068 doi:10.1074/jbc.M101305200
↑ Coffey AJ, Brooksbank RA, Brandau O, Oohashi T, Howell GR, Bye JM, Cahn AP, Durham J, Heath P, Wray P, Pavitt R, Wilkinson J, Leversha M, Huckle E, Shaw-Smith CJ, Dunham A, Rhodes S, Schuster V, Porta G, Yin L, Serafini P, Sylla B, Zollo M, Franco B, Bolino A, Seri M, Lanyi A, Davis JR, Webster D, Harris A, Lenoir G, de St Basile G, Jones A, Behloradsky BH, Achatz H, Murken J, Fassler R, Sumegi J, Romeo G, Vaudin M, Ross MT, Meindl A, Bentley DR. Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Nat Genet. 1998 Oct;20(2):129-35. PMID:9771704 doi:10.1038/2424
↑ Hwang PM, Li C, Morra M, Lillywhite J, Muhandiram DR, Gertler F, Terhorst C, Kay LE, Pawson T, Forman-Kay JD, Li SC. A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome. EMBO J. 2002 Feb 1;21(3):314-23. PMID:11823424 doi:10.1093/emboj/21.3.314
↑ Yin L, Ferrand V, Lavoue MF, Hayoz D, Philippe N, Souillet G, Seri M, Giacchino R, Castagnola E, Hodgson S, Sylla BS, Romeo G. SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients. Hum Genet. 1999 Nov;105(5):501-5. PMID:10598819
↑ Sumegi J, Huang D, Lanyi A, Davis JD, Seemayer TA, Maeda A, Klein G, Seri M, Wakiguchi H, Purtilo DT, Gross TG. Correlation of mutations of the SH2D1A gene and epstein-barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease. Blood. 2000 Nov 1;96(9):3118-25. PMID:11049992
↑ Benoit L, Wang X, Pabst HF, Dutz J, Tan R. Defective NK cell activation in X-linked lymphoproliferative disease. J Immunol. 2000 Oct 1;165(7):3549-53. PMID:11034354
↑ Sumazaki R, Kanegane H, Osaki M, Fukushima T, Tsuchida M, Matsukura H, Shinozaki K, Kimura H, Matsui A, Miyawaki T. SH2D1A mutations in Japanese males with severe Epstein-Barr virus--associated illnesses. Blood. 2001 Aug 15;98(4):1268-70. PMID:11493483
↑ Li C, Iosef C, Jia CY, Gkourasas T, Han VK, Shun-Cheng Li S. Disease-causing SAP mutants are defective in ligand binding and protein folding. Biochemistry. 2003 Dec 23;42(50):14885-92. PMID:14674764 doi:10.1021/bi034798l
↑ Erdos M, Uzvolgyi E, Nemes Z, Torok O, Rakoczi E, Went-Sumegi N, Sumegi J, Marodi L. Characterization of a new disease-causing mutation of SH2D1A in a family with X-linked lymphoproliferative disease. Hum Mutat. 2005 May;25(5):506. PMID:15841490 doi:10.1002/humu.9339
↑ Hare NJ, Ma CS, Alvaro F, Nichols KE, Tangye SG. Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP. Int Immunol. 2006 Jul;18(7):1055-65. Epub 2006 May 23. PMID:16720617 doi:dxl039

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1d4t"

@@ Line 3: / Line 3: @@
 <StructureSection load='1d4t' size='340' side='right'caption='[[1d4t]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1d4t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D4T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1d4t]] is a 2 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=1D4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D4T FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1d1z|1d1z]], [[1d4w|1d4w]]</div></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]] 1.1&#8491;</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=1d4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d4t OCA], [https://pdbe.org/1d4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d4t RCSB], [https://www.ebi.ac.uk/pdbsum/1d4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d4t ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN]] Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) [MIM:[https://omim.org/entry/308240 308240]]; also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:11477068</ref> <ref>PMID:9771704</ref> <ref>PMID:11823424</ref> <ref>PMID:10598819</ref> <ref>PMID:11049992</ref> <ref>PMID:11034354</ref> <ref>PMID:11493483</ref> <ref>PMID:14674764</ref> <ref>PMID:15841490</ref> <ref>PMID:16720617</ref>
+[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN] Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) [MIM:[https://omim.org/entry/308240 308240]; also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:11477068</ref> <ref>PMID:9771704</ref> <ref>PMID:11823424</ref> <ref>PMID:10598819</ref> <ref>PMID:11049992</ref> <ref>PMID:11034354</ref> <ref>PMID:11493483</ref> <ref>PMID:14674764</ref> <ref>PMID:15841490</ref> <ref>PMID:16720617</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN]] Inhibitor of the SLAM self-association. Acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. Mediates interaction between FYN and SLAMF1. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3. [[https://www.uniprot.org/uniprot/SLAF1_HUMAN SLAF1_HUMAN]] High-affinity self-ligand important in bidirectional T-cell to B-cell stimulation. SLAM-induced signal-transduction events in T-lymphocytes are different from those in B-cells. Two modes of SLAM signaling are likely to exist: one in which the inhibitor SH2D1A acts as a negative regulator and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction operates.
+[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN] Inhibitor of the SLAM self-association. Acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. Mediates interaction between FYN and SLAMF1. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 21: / Line 21: @@
 </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=1d4t ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I).
-Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition.,Poy F, Yaffe MB, Sayos J, Saxena K, Morra M, Sumegi J, Cantley LC, Terhorst C, Eck MJ Mol Cell. 1999 Oct;4(4):555-61. PMID:10549287<ref>PMID:10549287</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 1d4t" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Eck, M J]]
+[[Category: Eck MJ]]
-[[Category: Poy, F]]
+[[Category: Poy F]]
-[[Category: Saxena, K]]
+[[Category: Saxena K]]
-[[Category: Sayos, J]]
+[[Category: Sayos J]]
-[[Category: Yaffe, M B]]
+[[Category: Yaffe MB]]
-[[Category: Peptide recognition]]
-[[Category: Sh2 domain]]
-[[Category: Signal transduction]]
-[[Category: Signaling protein]]
-[[Category: Tyrosine kinase]]

1d4t

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH A SLAM PEPTIDE

Structural highlights

Disease

Function

Evolutionary Conservation

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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