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| - | {{STRUCTURE_4a5x| PDB=4a5x | SCENE= }} | |
| - | ===Structures of MITD1=== | |
| - | {{ABSTRACT_PUBMED_23045692}} | |
| | | | |
| - | ==Function== | + | ==Structures of MITD1== |
| - | [[http://www.uniprot.org/uniprot/MITD1_HUMAN MITD1_HUMAN]] Required for efficient abscission at the end of cytokinesis, together with components of the ESCRT-III complex.<ref>PMID:23015756</ref> <ref>PMID:23045692</ref> [[http://www.uniprot.org/uniprot/CHM1A_HUMAN CHM1A_HUMAN]] Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing.<ref>PMID:8863740</ref> <ref>PMID:11559747</ref> <ref>PMID:11559748</ref> <ref>PMID:19129479</ref> <ref>PMID:23045692</ref> | + | <StructureSection load='4a5x' size='340' side='right'caption='[[4a5x]], [[Resolution|resolution]] 1.91Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[4a5x]] 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=4A5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A5X 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]] 1.91Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=P15:2,5,8,11,14,17-HEXAOXANONADECAN-19-OL'>P15</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=4a5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5x OCA], [https://pdbe.org/4a5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a5x RCSB], [https://www.ebi.ac.uk/pdbsum/4a5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a5x ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MITD1_HUMAN MITD1_HUMAN] Required for efficient abscission at the end of cytokinesis, together with components of the ESCRT-III complex.<ref>PMID:23015756</ref> <ref>PMID:23045692</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain containing protein 1 (MITD1). Crystal structures of MITD1 reveal a dimer, with a microtubule-interacting and trafficking (MIT) domain at the N terminus and a unique, unanticipated phospholipase D-like (PLD) domain at the C terminus that binds membranes. We show that the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis. Depletion of MITD1 causes a distinct cytokinetic phenotype consistent with destabilization of the midbody and abscission failure. These results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division. |
| | | | |
| - | ==About this Structure==
| + | ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes.,Hadders MA, Agromayor M, Obita T, Perisic O, Caballe A, Kloc M, Lamers MH, Williams RL, Martin-Serrano J Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045692<ref>PMID:23045692</ref> |
| - | [[4a5x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A5X OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | <ref group="xtra">PMID:023045692</ref><references group="xtra"/><references/> | + | </div> |
| - | [[Category: Human]] | + | <div class="pdbe-citations 4a5x" style="background-color:#fffaf0;"></div> |
| - | [[Category: Agromayor, M.]] | + | == References == |
| - | [[Category: Caballe, A.]] | + | <references/> |
| - | [[Category: Hadders, M A.]] | + | __TOC__ |
| - | [[Category: Martin-Serrano, J.]] | + | </StructureSection> |
| - | [[Category: Obita, T.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Perisic, O.]] | + | [[Category: Large Structures]] |
| - | [[Category: Williams, R L.]] | + | [[Category: Agromayor M]] |
| - | [[Category: Cytokinesis]]
| + | [[Category: Caballe A]] |
| - | [[Category: Escrt]]
| + | [[Category: Hadders MA]] |
| - | [[Category: Midbody]]
| + | [[Category: Martin-Serrano J]] |
| - | [[Category: Protein transport]]
| + | [[Category: Obita T]] |
| | + | [[Category: Perisic O]] |
| | + | [[Category: Williams RL]] |
| Structural highlights
Function
MITD1_HUMAN Required for efficient abscission at the end of cytokinesis, together with components of the ESCRT-III complex.[1] [2]
Publication Abstract from PubMed
The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain containing protein 1 (MITD1). Crystal structures of MITD1 reveal a dimer, with a microtubule-interacting and trafficking (MIT) domain at the N terminus and a unique, unanticipated phospholipase D-like (PLD) domain at the C terminus that binds membranes. We show that the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis. Depletion of MITD1 causes a distinct cytokinetic phenotype consistent with destabilization of the midbody and abscission failure. These results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division.
ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes.,Hadders MA, Agromayor M, Obita T, Perisic O, Caballe A, Kloc M, Lamers MH, Williams RL, Martin-Serrano J Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045692[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee S, Chang J, Renvoise B, Tipirneni A, Yang S, Blackstone C. MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis. Mol Biol Cell. 2012 Nov;23(22):4347-61. doi: 10.1091/mbc.E12-04-0292. Epub 2012, Sep 26. PMID:23015756 doi:http://dx.doi.org/10.1091/mbc.E12-04-0292
- ↑ Hadders MA, Agromayor M, Obita T, Perisic O, Caballe A, Kloc M, Lamers MH, Williams RL, Martin-Serrano J. ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes. Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045692 doi:http://dx.doi.org/10.1073/pnas.1206839109
- ↑ Hadders MA, Agromayor M, Obita T, Perisic O, Caballe A, Kloc M, Lamers MH, Williams RL, Martin-Serrano J. ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes. Proc Natl Acad Sci U S A. 2012 Oct 8. PMID:23045692 doi:http://dx.doi.org/10.1073/pnas.1206839109
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