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| - | [[Image:2no2.gif|left|200px]]<br /> | |
| - | <applet load="2no2" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2no2, resolution 2.800Å" /> | |
| - | '''Crystal structure of the DLLRKN-containing coiled-coil domain of Huntingtin-interacting protein 1'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure of the DLLRKN-containing coiled-coil domain of Huntingtin-interacting protein 1== |
| - | 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. | + | <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. |
| | | | |
| - | ==Disease==
| + | 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> |
| - | Known disease associated with this structure: Prostate cancer, progression of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601767 601767]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 2NO2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2NO2 OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 2no2" style="background-color:#fffaf0;"></div> |
| - | ==Reference== | + | == References == |
| - | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17257618 17257618]
| + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Helms, S.]] | + | [[Category: Helms S]] |
| - | [[Category: Mishra, S.]] | + | [[Category: Mishra S]] |
| - | [[Category: Nix, J.]] | + | [[Category: Nix J]] |
| - | [[Category: Ybe, J.A.]] | + | [[Category: Ybe JA]] |
| - | [[Category: cell adhesion]]
| + | |
| - | [[Category: clathrin light chain binding; hip1 coiled-coil domain; endocytosis; clathrin self-assembly]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:00:29 2007''
| + | |
| Structural highlights
Disease
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
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.[1] [2] [3] [4] [5] [6] [7] [8]
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
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[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, Tait D, Colicelli J, Lehrach H. HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system. Hum Mol Genet. 1997 Mar;6(3):487-95. PMID:9147654
- ↑ Hackam AS, Yassa AS, Singaraja R, Metzler M, Gutekunst CA, Gan L, Warby S, Wellington CL, Vaillancourt J, Chen N, Gervais FG, Raymond L, Nicholson DW, Hayden MR. Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. J Biol Chem. 2000 Dec 29;275(52):41299-308. PMID:11007801 doi:10.1074/jbc.M008408200
- ↑ Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE. The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Hum Mol Genet. 2001 Aug 15;10(17):1807-17. PMID:11532990
- ↑ Mishra SK, Agostinelli NR, Brett TJ, Mizukami I, Ross TS, Traub LM. Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins. J Biol Chem. 2001 Dec 7;276(49):46230-6. Epub 2001 Sep 27. PMID:11577110 doi:10.1074/jbc.M108177200
- ↑ Legendre-Guillemin V, Metzler M, Charbonneau M, Gan L, Chopra V, Philie J, Hayden MR, McPherson PS. HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. J Biol Chem. 2002 May 31;277(22):19897-904. Epub 2002 Mar 11. PMID:11889126 doi:10.1074/jbc.M112310200
- ↑ Rao DS, Hyun TS, Kumar PD, Mizukami IF, Rubin MA, Lucas PC, Sanda MG, Ross TS. Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival. J Clin Invest. 2002 Aug;110(3):351-60. PMID:12163454 doi:10.1172/JCI15529
- ↑ Hyun TS, Rao DS, Saint-Dic D, Michael LE, Kumar PD, Bradley SV, Mizukami IF, Oravecz-Wilson KI, Ross TS. HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains. J Biol Chem. 2004 Apr 2;279(14):14294-306. Epub 2004 Jan 19. PMID:14732715 doi:10.1074/jbc.M312645200
- ↑ Mills IG, Gaughan L, Robson C, Ross T, McCracken S, Kelly J, Neal DE. Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors. J Cell Biol. 2005 Jul 18;170(2):191-200. PMID:16027218 doi:10.1083/jcb.200503106
- ↑ Ybe JA, Mishra S, Helms S, Nix J. 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. J Mol Biol. 2007 Mar 16;367(1):8-15. Epub 2006 Dec 23. PMID:17257618 doi:10.1016/j.jmb.2006.12.052
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