1hcf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:29, 6 November 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1hcf.jpg|left|200px]]
 
-
{{Structure
+
==Crystal structure of TrkB-d5 bound to neurotrophin-4/5==
-
|PDB= 1hcf |SIZE=350|CAPTION= <scene name='initialview01'>1hcf</scene>, resolution 2.7&Aring;
+
<StructureSection load='1hcf' size='340' side='right'caption='[[1hcf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
+
<table><tr><td colspan='2'>[[1hcf]] is a 4 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=1HCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HCF FirstGlance]. <br>
-
|ACTIVITY=
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
-
|GENE=
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1hcf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hcf OCA], [https://pdbe.org/1hcf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hcf RCSB], [https://www.ebi.ac.uk/pdbsum/1hcf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hcf ProSAT]</span></td></tr>
-
 
+
</table>
-
'''CRYSTAL STRUCTURE OF TRKB-D5 BOUND TO NEUROTROPHIN-4/5'''
+
== Disease ==
-
 
+
[https://www.uniprot.org/uniprot/NTF4_HUMAN NTF4_HUMAN] Defects in NTF4 may be associated with susceptibility to primary open angle glaucoma type 1O (GLC1O) [MIM:[https://omim.org/entry/613100 613100]. A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.
-
 
+
== Function ==
-
==Overview==
+
[https://www.uniprot.org/uniprot/NTF4_HUMAN NTF4_HUMAN] Target-derived survival factor for peripheral sensory sympathetic 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/hc/1hcf_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=1hcf ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
BACKGROUND: The binding of neurotrophin ligands to their respective Trk cellular receptors initiates intracellular signals essential for the growth and survival of neurons. The site of neurotrophin binding has been located to the fifth extracellular domain of the Trk receptor, with this region regulating both the affinity and specificity of Trk receptor:neurotrophin interaction. Neurotrophin function has been implicated in a number of neurological disorders, including Alzheimer's disease and Parkinson's disease. RESULTS: We have determined the 2.7 A crystal structure of neurotrophin-4/5 bound to the neurotrophin binding domain of its high-affinity receptor TrkB (TrkB-d5). As previously seen in the interaction of nerve growth factor with TrkA, neurotrophin-4/5 forms a crosslink between two spatially distant receptor molecules. The contacts formed in the TrkB-d5:neurotrophin-4/5 complex can be divided into a conserved area similar to a region observed in the TrkA-d5:NGF complex and a second site-unique in each ligand-receptor pair-formed primarily by the ordering of the neurotrophin N terminus. CONCLUSIONS: Together, the structures of the TrkB-d5:NT-4/5 and TrkA-d5:NGF complexes confirm a consistent pattern of recognition in Trk receptor:neurotrophin complex formation. In both cases, the N terminus of the neurotrophin becomes ordered only on complex formation. This ordering appears to be directed largely by the receptor surface, with the resulting complementary surfaces providing the main determinant of receptor specificity. These features provide an explanation both for the limited crossreactivity observed between the range of neurotrophins and Trk receptors and for the high-affinity binding associated with respective ligand-receptor pairs.
BACKGROUND: The binding of neurotrophin ligands to their respective Trk cellular receptors initiates intracellular signals essential for the growth and survival of neurons. The site of neurotrophin binding has been located to the fifth extracellular domain of the Trk receptor, with this region regulating both the affinity and specificity of Trk receptor:neurotrophin interaction. Neurotrophin function has been implicated in a number of neurological disorders, including Alzheimer's disease and Parkinson's disease. RESULTS: We have determined the 2.7 A crystal structure of neurotrophin-4/5 bound to the neurotrophin binding domain of its high-affinity receptor TrkB (TrkB-d5). As previously seen in the interaction of nerve growth factor with TrkA, neurotrophin-4/5 forms a crosslink between two spatially distant receptor molecules. The contacts formed in the TrkB-d5:neurotrophin-4/5 complex can be divided into a conserved area similar to a region observed in the TrkA-d5:NGF complex and a second site-unique in each ligand-receptor pair-formed primarily by the ordering of the neurotrophin N terminus. CONCLUSIONS: Together, the structures of the TrkB-d5:NT-4/5 and TrkA-d5:NGF complexes confirm a consistent pattern of recognition in Trk receptor:neurotrophin complex formation. In both cases, the N terminus of the neurotrophin becomes ordered only on complex formation. This ordering appears to be directed largely by the receptor surface, with the resulting complementary surfaces providing the main determinant of receptor specificity. These features provide an explanation both for the limited crossreactivity observed between the range of neurotrophins and Trk receptors and for the high-affinity binding associated with respective ligand-receptor pairs.
-
==Disease==
+
Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5.,Banfield MJ, Naylor RL, Robertson AG, Allen SJ, Dawbarn D, Brady RL Structure. 2001 Dec;9(12):1191-9. PMID:11738045<ref>PMID:11738045</ref>
-
Known diseases associated with this structure: Obesity, hyperphagia, and developmental delay OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600456 600456]]
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
1HCF is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HCF OCA].
+
</div>
 +
<div class="pdbe-citations 1hcf" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5., Banfield MJ, Naylor RL, Robertson AG, Allen SJ, Dawbarn D, Brady RL, Structure. 2001 Dec;9(12):1191-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11738045 11738045]
+
*[[Neurotrophin|Neurotrophin]]
 +
*[[Neutrotrophin|Neutrotrophin]]
 +
*[[TrkB tyrosine kinase receptor|TrkB tyrosine kinase receptor]]
 +
*[[Tyrosine kinase receptor 3D structures|Tyrosine kinase receptor 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
-
[[Category: Allen, S J.]]
+
[[Category: Allen SJ]]
-
[[Category: Banfield, M J.]]
+
[[Category: Banfield MJ]]
-
[[Category: Brady, R L.]]
+
[[Category: Brady RL]]
-
[[Category: Dawbarn, D.]]
+
[[Category: Dawbarn D]]
-
[[Category: Naylor, R L.]]
+
[[Category: Naylor RL]]
-
[[Category: Robertson, A G.S.]]
+
[[Category: Robertson AGS]]
-
[[Category: SO4]]
+
-
[[Category: immunoglobulin domain]]
+
-
[[Category: neurotrophin-4/5]]
+
-
[[Category: ngf-beta superfamily]]
+
-
[[Category: trkb receptor]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:35:20 2008''
+

Current revision

Crystal structure of TrkB-d5 bound to neurotrophin-4/5

PDB ID 1hcf

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/1hcf"
Personal tools