1sg1

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

Structural highlights

1sg1 is a 3 chain structure with sequence from Homo sapiens and Rattus norvegicus. The August 2005 RCSB PDB Molecule of the Month feature on Neurotrophins by David S. Goodsell is 10.2210/rcsb_pdb/mom_2005_8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:CL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NGF_HUMAN Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM: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.[1] [2] [3]

Function

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.

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

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.

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[4]

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

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Citations
50 reviews cite this structure
Neurotrophin-regulated signalling pathways.
Reichardt et al. (2006)
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101 other articles
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See Also

References

  1. ↑ Einarsdottir E, Carlsson A, Minde J, Toolanen G, Svensson O, Solders G, Holmgren G, Holmberg D, Holmberg M. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum Mol Genet. 2004 Apr 15;13(8):799-805. Epub 2004 Feb 19. PMID:14976160 doi:10.1093/hmg/ddh096
  2. ↑ Carvalho OP, Thornton GK, Hertecant J, Houlden H, Nicholas AK, Cox JJ, Rielly M, Al-Gazali L, Woods CG. A novel NGF mutation clarifies the molecular mechanism and extends the phenotypic spectrum of the HSAN5 neuropathy. J Med Genet. 2011 Feb;48(2):131-5. doi: 10.1136/jmg.2010.081455. Epub 2010 Oct, 26. PMID:20978020 doi:10.1136/jmg.2010.081455
  3. ↑ Davidson G, Murphy S, Polke J, Laura M, Salih M, Muntoni F, Blake J, Brandner S, Davies N, Horvath R, Price S, Donaghy M, Roberts M, Foulds N, Ramdharry G, Soler D, Lunn M, Manji H, Davis M, Houlden H, Reilly M. Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. J Neurol. 2012 Aug;259(8):1673-85. PMID:22302274 doi:10.1007/s00415-011-6397-y
  4. ↑ He XL, Garcia KC. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science. 2004 May 7;304(5672):870-5. PMID:15131306 doi:10.1126/science.1095190

Contents


PDB ID 1sg1

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OCA

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