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| | <StructureSection load='2e3h' size='340' side='right'caption='[[2e3h]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='2e3h' size='340' side='right'caption='[[2e3h]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2e3h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2e3h]] 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=2E3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E3H FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2e3i|2e3i]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLIP-170 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2e3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e3h OCA], [https://pdbe.org/2e3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e3h RCSB], [https://www.ebi.ac.uk/pdbsum/2e3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e3h ProSAT]</span></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=2e3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e3h OCA], [https://pdbe.org/2e3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e3h RCSB], [https://www.ebi.ac.uk/pdbsum/2e3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e3h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/REST_HUMAN REST_HUMAN]] Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, mSin3 and CoREST, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier.<ref>PMID:7697725</ref> <ref>PMID:7871435</ref> <ref>PMID:8568247</ref> <ref>PMID:12399542</ref>
| + | [https://www.uniprot.org/uniprot/CLIP1_HUMAN CLIP1_HUMAN] Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking.<ref>PMID:12433698</ref> <ref>PMID:17889670</ref> <ref>PMID:17563362</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2e3h" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2e3h" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[CAP-Gly domain|CAP-Gly domain]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hakoshima, T]] | + | [[Category: Hakoshima T]] |
| - | [[Category: Maesaki, R]] | + | [[Category: Maesaki R]] |
| - | [[Category: Cap-gly]]
| + | |
| - | [[Category: Cytoplasmic linker]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Tubulin binding]]
| + | |
| Structural highlights
Function
CLIP1_HUMAN Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking.[1] [2] [3]
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
Cytoplasmic linker protein 170 (CLIP-170) is a prototype of the plus end-tracking proteins that regulate microtubule dynamics, but it is obscure how CLIP-170 recognizes the microtubule plus end and contributes to polymerization rescue. Crystallographic, NMR, and mutation studies of two tandem cytoskeleton-associated protein glycine-rich (CAP-Gly) domains of CLIP-170, CAP-Gly-1 and CAP-Gly-2, revealed positively charged basic grooves of both CAP-Gly domains for tubulin binding, whereas the CAP-Gly-2 domain possesses a more basic groove and directly binds the EExEEY/F motif of the C-terminal acidic-tail ends of alpha-tubulin. Notably, the p150(Glued) CAP-Gly domain that is furnished with a less positively charged surface only weakly interacts with the alpha-tubulin acidic tail. Mutation studies showed that this acidic sextette motif is the minimum region for CAP-Gly binding. The C-terminal zinc knuckle domains of CLIP-170 bind the basic groove to inhibit the binding to the acidic tails. These results provide a structural basis for the proposed CLIP-170 copolymerization with tubulin on the microtubule plus end. CLIP-170 strongly binds the acidic tails of EB1 as well as those of alpha-tubulins, indicating that EB1 localized at the plus end contributes to CLIP-170 recruitment to the plus end. We suggest that CLIP-170 stimulates microtubule polymerization and/or nucleation by neutralizing the negative charges of tubulins with the highly positive charges of the CLIP-170 CAP-Gly domains. Once CLIP-170 binds microtubule, the released zinc knuckle domain may serve to recruit dynein to the plus end by interacting with p150(Glued) and LIS1. Thus, our structures provide the structural basis for the specific dynein loading on the microtubule plus end.
Structural basis for tubulin recognition by cytoplasmic linker protein 170 and its autoinhibition.,Mishima M, Maesaki R, Kasa M, Watanabe T, Fukata M, Kaibuchi K, Hakoshima T Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10346-51. Epub 2007 Jun 11. PMID:17563362[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sahin U, Neumann F, Tureci O, Schmits R, Perez F, Pfreundschuh M. Hodgkin and Reed-Sternberg cell-associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells. Blood. 2002 Dec 1;100(12):4139-45. PMID:12433698 doi:10.1182/blood.V100.12.4139
- ↑ Slep KC, Vale RD. Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1. Mol Cell. 2007 Sep 21;27(6):976-91. PMID:17889670 doi:10.1016/j.molcel.2007.07.023
- ↑ Mishima M, Maesaki R, Kasa M, Watanabe T, Fukata M, Kaibuchi K, Hakoshima T. Structural basis for tubulin recognition by cytoplasmic linker protein 170 and its autoinhibition. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10346-51. Epub 2007 Jun 11. PMID:17563362
- ↑ Mishima M, Maesaki R, Kasa M, Watanabe T, Fukata M, Kaibuchi K, Hakoshima T. Structural basis for tubulin recognition by cytoplasmic linker protein 170 and its autoinhibition. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10346-51. Epub 2007 Jun 11. PMID:17563362
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