2no2
From Proteopedia
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| - | [[Image:2no2.gif|left|200px]] | ||
| - | + | ==Crystal structure of the DLLRKN-containing coiled-coil domain of Huntingtin-interacting protein 1== | |
| - | + | <StructureSection load='2no2' size='340' side='right'caption='[[2no2]], [[Resolution|resolution]] 2.80Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2no2]] 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=2NO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NO2 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]] 2.8Å</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=2no2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2no2 OCA], [https://pdbe.org/2no2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2no2 RCSB], [https://www.ebi.ac.uk/pdbsum/2no2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2no2 ProSAT]</span></td></tr> |
| - | + | </table> | |
| - | + | == Disease == | |
| - | + | [https://www.uniprot.org/uniprot/HIP1_HUMAN HIP1_HUMAN] Note=A chromosomal aberration involving HIP1 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;7)(q33;q11.2) with PDGFRB. The chimeric HIP1-PDGFRB transcript results from an in-frame fusion of the two genes. The reciprocal PDGFRB-HIP1 transcript is not expressed. | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/HIP1_HUMAN HIP1_HUMAN] Plays a role in clathrin-mediated endocytosis and trafficking. Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner. Enhances androgen receptor (AR)-mediated transcription. May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. May play a functional role in the cell filament networks. May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors.<ref>PMID:9147654</ref> <ref>PMID:11007801</ref> <ref>PMID:11532990</ref> <ref>PMID:11577110</ref> <ref>PMID:11889126</ref> <ref>PMID:12163454</ref> <ref>PMID:14732715</ref> <ref>PMID:16027218</ref> | |
| - | == | + | == 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/no/2no2_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2no2 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Huntingtin interacting protein 1 (HIP1) is a member of a family of proteins whose interaction with Huntingtin is critical to prevent cells from initiating apoptosis. HIP1, and related protein HIP12/1R, can also bind to clathrin and membrane phospholipids, and HIP12/1R links the CCV to the actin cytoskeleton. HIP1 and HIP12/1R interact with the clathrin light chain EED regulatory site and stimulate clathrin lattice assembly. Here, we report the X-ray structure of the coiled-coil domain of HIP1 (residues 482-586) that includes residues crucial for binding clathrin light chain. The dimeric HIP1 crystal structure is partially splayed open. The comparison of the HIP1 model with coiled-coil predictions revealed the heptad repeat in the dimeric trunk (S2 path) is offset relative to the register of the heptad repeat from the N-terminal portion (S1 path) of the molecule. Furthermore, surface analysis showed there is a third hydrophobic path (S3) running parallel with S1 and S2. We present structural evidence supporting a role for the S3 path as an interaction surface for clathrin light chain. Finally, comparative analysis suggests the mode of binding between sla2p and clathrin light chain may be different in yeast. | Huntingtin interacting protein 1 (HIP1) is a member of a family of proteins whose interaction with Huntingtin is critical to prevent cells from initiating apoptosis. HIP1, and related protein HIP12/1R, can also bind to clathrin and membrane phospholipids, and HIP12/1R links the CCV to the actin cytoskeleton. HIP1 and HIP12/1R interact with the clathrin light chain EED regulatory site and stimulate clathrin lattice assembly. Here, we report the X-ray structure of the coiled-coil domain of HIP1 (residues 482-586) that includes residues crucial for binding clathrin light chain. The dimeric HIP1 crystal structure is partially splayed open. The comparison of the HIP1 model with coiled-coil predictions revealed the heptad repeat in the dimeric trunk (S2 path) is offset relative to the register of the heptad repeat from the N-terminal portion (S1 path) of the molecule. Furthermore, surface analysis showed there is a third hydrophobic path (S3) running parallel with S1 and S2. We present structural evidence supporting a role for the S3 path as an interaction surface for clathrin light chain. Finally, comparative analysis suggests the mode of binding between sla2p and clathrin light chain may be different in yeast. | ||
| - | + | Crystal structure at 2.8 A of the DLLRKN-containing coiled-coil domain of huntingtin-interacting protein 1 (HIP1) reveals a surface suitable for clathrin light chain binding.,Ybe JA, Mishra S, Helms S, Nix J J Mol Biol. 2007 Mar 16;367(1):8-15. Epub 2006 Dec 23. PMID:17257618<ref>PMID:17257618</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 2no2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Helms | + | [[Category: Helms S]] |
| - | [[Category: Mishra | + | [[Category: Mishra S]] |
| - | [[Category: Nix | + | [[Category: Nix J]] |
| - | [[Category: Ybe | + | [[Category: Ybe JA]] |
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Current revision
Crystal structure of the DLLRKN-containing coiled-coil domain of Huntingtin-interacting protein 1
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Categories: Homo sapiens | Large Structures | Helms S | Mishra S | Nix J | Ybe JA
