1nt3: Difference between revisions
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< | ==HUMAN NEUROTROPHIN-3== | ||
<StructureSection load='1nt3' size='340' side='right'caption='[[1nt3]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1nt3]] is a 1 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=1NT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NT3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=1nt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nt3 OCA], [https://pdbe.org/1nt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nt3 RCSB], [https://www.ebi.ac.uk/pdbsum/1nt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nt3 ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NTF3_HUMAN NTF3_HUMAN] Seems to promote the survival of visceral and proprioceptive sensory neurons. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nt/1nt3_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=1nt3 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Neurotrophin-3 (NT-3) is a cystine knot growth factor that promotes the survival, proliferation, and differentiation of developing neurons and is a potential therapeutic for neurodegenerative diseases. To clarify the structural basis of receptor specificity and the role of neurotrophin dimerization in receptor activation, the structure of the NT-3 homodimer was determined using X-ray crystallography. The orthorhombic crystals diffract to 2.4 A, with dimer symmetry occurring about a crystallographic 2-fold axis. The overall structure of NT-3 resembles that of the other neurotrophins, NGF and BDNF; each protomer forms a twisted four-stranded beta sheet, with three intertwined disulfide bonds. There are notable differences, however, between NT-3 and NGF in the surface loops and in three functionally important regions, shown in previous mutagenesis studies to be critical for binding. One such difference implies that NT-3's binding affinity and specificity depend on a novel hydrogen bond between Gln 83, a residue important for binding specificity with TrkC, and Arg 103, a residue crucial for binding affinity with TrkC. NT-3's extensive dimer interface buries much of the otherwise solvent-accessible hydrophobic surface area and suggests that the dimeric state is stabilized through the formation of this hydrophobic core. A comparison of the dimer interface between the NT-3 homodimer and the BDNF/NT-3 heterodimer reveals similar patterns of hydrogen bonds and nonpolar contacts, which reinforces the notion that the evolutionarily conserved neurotrophin interface resulted from the need for receptor dimerization in signal initiation. | |||
Crystal structure of neurotrophin-3 homodimer shows distinct regions are used to bind its receptors.,Butte MJ, Hwang PK, Mobley WC, Fletterick RJ Biochemistry. 1998 Dec 1;37(48):16846-52. PMID:9836577<ref>PMID:9836577</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1nt3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Neurotrophin|Neurotrophin]] | |||
*[[Neutrotrophin|Neutrotrophin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[ | |||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Butte MJ]] | ||
[[Category: | [[Category: Fletterick RJ]] | ||
[[Category: | [[Category: Hwang PK]] | ||
[[Category: | [[Category: Mobley WC]] | ||
Latest revision as of 03:18, 21 November 2024
HUMAN NEUROTROPHIN-3HUMAN NEUROTROPHIN-3
Structural highlights
FunctionNTF3_HUMAN Seems to promote the survival of visceral and proprioceptive sensory neurons. 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 PubMedNeurotrophin-3 (NT-3) is a cystine knot growth factor that promotes the survival, proliferation, and differentiation of developing neurons and is a potential therapeutic for neurodegenerative diseases. To clarify the structural basis of receptor specificity and the role of neurotrophin dimerization in receptor activation, the structure of the NT-3 homodimer was determined using X-ray crystallography. The orthorhombic crystals diffract to 2.4 A, with dimer symmetry occurring about a crystallographic 2-fold axis. The overall structure of NT-3 resembles that of the other neurotrophins, NGF and BDNF; each protomer forms a twisted four-stranded beta sheet, with three intertwined disulfide bonds. There are notable differences, however, between NT-3 and NGF in the surface loops and in three functionally important regions, shown in previous mutagenesis studies to be critical for binding. One such difference implies that NT-3's binding affinity and specificity depend on a novel hydrogen bond between Gln 83, a residue important for binding specificity with TrkC, and Arg 103, a residue crucial for binding affinity with TrkC. NT-3's extensive dimer interface buries much of the otherwise solvent-accessible hydrophobic surface area and suggests that the dimeric state is stabilized through the formation of this hydrophobic core. A comparison of the dimer interface between the NT-3 homodimer and the BDNF/NT-3 heterodimer reveals similar patterns of hydrogen bonds and nonpolar contacts, which reinforces the notion that the evolutionarily conserved neurotrophin interface resulted from the need for receptor dimerization in signal initiation. Crystal structure of neurotrophin-3 homodimer shows distinct regions are used to bind its receptors.,Butte MJ, Hwang PK, Mobley WC, Fletterick RJ Biochemistry. 1998 Dec 1;37(48):16846-52. PMID:9836577[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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