1sg1

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{{STRUCTURE_1sg1| PDB=1sg1 | SCENE= }}
 
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===Crystal Structure of the Receptor-Ligand Complex between Nerve Growth Factor and the Common Neurotrophin Receptor p75===
 
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{{ABSTRACT_PUBMED_15131306}}
 
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==Disease==
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==Crystal Structure of the Receptor-Ligand Complex between Nerve Growth Factor and the Common Neurotrophin Receptor p75==
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[[http://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN]] Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM:[http://omim.org/entry/608654 608654]]. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable.<ref>PMID:14976160</ref><ref>PMID:20978020</ref><ref>PMID:22302274</ref>
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<StructureSection load='1sg1' size='340' side='right'caption='[[1sg1]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1sg1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. The August 2005 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Neurotrophins'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2005_8 10.2210/rcsb_pdb/mom_2005_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SG1 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1sg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sg1 OCA], [https://pdbe.org/1sg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sg1 RCSB], [https://www.ebi.ac.uk/pdbsum/1sg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sg1 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN] Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM:[https://omim.org/entry/608654 608654]. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable.<ref>PMID:14976160</ref> <ref>PMID:20978020</ref> <ref>PMID:22302274</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sg/1sg1_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1sg1 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Neurotrophins are secreted growth factors critical for the development and maintenance of the vertebrate nervous system. Neurotrophins activate two types of cell surface receptors, the Trk receptor tyrosine kinases and the shared p75 neurotrophin receptor. We have determined the 2.4 A crystal structure of the prototypic neurotrophin, nerve growth factor (NGF), complexed with the extracellular domain of p75. Surprisingly, the complex is composed of an NGF homodimer asymmetrically bound to a single p75. p75 binds along the homodimeric interface of NGF, which disables NGF's symmetry-related second p75 binding site through an allosteric conformational change. Thus, neurotrophin signaling through p75 may occur by disassembly of p75 dimers and assembly of asymmetric 2:1 neurotrophin/p75 complexes, which could potentially engage a Trk receptor to form a trimolecular signaling complex.
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==Function==
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Structure of nerve growth factor complexed with the shared neurotrophin receptor p75.,He XL, Garcia KC Science. 2004 May 7;304(5672):870-5. PMID:15131306<ref>PMID:15131306</ref>
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[[http://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN]] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival. [[http://www.uniprot.org/uniprot/TNR16_RAT TNR16_RAT]] Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1sg1]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. The August 2005 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Neurotrophins'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2005_8 10.2210/rcsb_pdb/mom_2005_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SG1 OCA].
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</div>
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<div class="pdbe-citations 1sg1" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:015131306</ref><references group="xtra"/><references/>
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*[[Nerve growth factor|Nerve growth factor]]
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*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Neurotrophins]]
[[Category: Neurotrophins]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Garcia, K C.]]
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[[Category: Garcia KC]]
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[[Category: He, X L.]]
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[[Category: He XL]]
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[[Category: Common neurotrophin receptor]]
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[[Category: Growth factor receptor]]
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[[Category: Hormone-growth factor-membrane protein complex]]
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[[Category: Nerve growth factor]]
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[[Category: Neurotrophin]]
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[[Category: Ngf]]
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[[Category: P75]]
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[[Category: Receptor-ligand complex]]
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Current revision

Crystal Structure of the Receptor-Ligand Complex between Nerve Growth Factor and the Common Neurotrophin Receptor p75

PDB ID 1sg1

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