|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the complex of Spartin MIT and IST1 MIM== | | ==Structure of the complex of Spartin MIT and IST1 MIM== |
| - | <StructureSection load='4u7i' size='340' side='right' caption='[[4u7i]], [[Resolution|resolution]] 1.79Å' scene=''> | + | <StructureSection load='4u7i' size='340' side='right'caption='[[4u7i]], [[Resolution|resolution]] 1.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u7i]] is a 2 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=4U7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U7I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u7i]] is a 2 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=4U7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U7I FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u7e|4u7e]], [[4u7y|4u7y]]</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]] 1.794Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPG20, KIAA0610, TAHCCP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IST1, KIAA0174 ([http://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=4u7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u7i OCA], [https://pdbe.org/4u7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u7i RCSB], [https://www.ebi.ac.uk/pdbsum/4u7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u7i ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u7i OCA], [http://pdbe.org/4u7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u7i RCSB], [http://www.ebi.ac.uk/pdbsum/4u7i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u7i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SPG20_HUMAN SPG20_HUMAN]] Defects in SPG20 are the cause of spastic paraplegia autosomal recessive type 20 (SPG20) [MIM:[http://omim.org/entry/275900 275900]]; also known as Troyer syndrome (TRS). Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG20 is characterized by dysarthria, distal amyotrophy, mild developmental delay and short stature.<ref>PMID:12134148</ref> | + | [https://www.uniprot.org/uniprot/SPART_HUMAN SPART_HUMAN] Autosomal recessive spastic paraplegia type 20. The disease is caused by variants affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPG20_HUMAN SPG20_HUMAN]] May be implicated in endosomal trafficking, or microtubule dynamics, or both.<ref>PMID:12676568</ref> [[http://www.uniprot.org/uniprot/IST1_HUMAN IST1_HUMAN]] Proposed to be involved in specific functions of the ESCRT machinery. Is required for efficient abscission during cytokinesis, but not for HIV-1 budding. The involvement in the MVB pathway is not established. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells.<ref>PMID:19129479</ref> <ref>PMID:19129480</ref> | + | [https://www.uniprot.org/uniprot/SPART_HUMAN SPART_HUMAN] May be implicated in endosomal trafficking, or microtubule dynamics, or both. Participates in cytokinesis (PubMed:20719964).<ref>PMID:20719964</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Guo, E Z]] | + | [[Category: Large Structures]] |
| - | [[Category: Xu, Z]] | + | [[Category: Guo EZ]] |
| - | [[Category: Complex]] | + | [[Category: Xu Z]] |
| - | [[Category: Mim3]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| Structural highlights
Disease
SPART_HUMAN Autosomal recessive spastic paraplegia type 20. The disease is caused by variants affecting the gene represented in this entry.
Function
SPART_HUMAN May be implicated in endosomal trafficking, or microtubule dynamics, or both. Participates in cytokinesis (PubMed:20719964).[1]
Publication Abstract from PubMed
The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multi-vesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the Microtubule Interacting and Trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-Interacting Motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5 and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode.
Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport (ESCRT)-III Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains.,Guo EZ, Xu Z J Biol Chem. 2015 Feb 5. pii: jbc.M114.607903. PMID:25657007[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Renvoisé B, Parker RL, Yang D, Bakowska JC, Hurley JH, Blackstone C. SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis. Mol Biol Cell. 2010 Oct 1;21(19):3293-303. PMID:20719964 doi:10.1091/mbc.E09-10-0879
- ↑ Guo EZ, Xu Z. Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport (ESCRT)-III Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains. J Biol Chem. 2015 Feb 5. pii: jbc.M114.607903. PMID:25657007 doi:http://dx.doi.org/10.1074/jbc.M114.607903
|
