4u7i

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Revision as of 12:07, 6 November 2017

Structure of the complex of Spartin MIT and IST1 MIM

Structural highlights

4u7i is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4u7e, 4u7y
Gene:	SPG20, KIAA0610, TAHCCP1 (HUMAN), IST1, KIAA0174 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SPG20_HUMAN] Defects in SPG20 are the cause of spastic paraplegia autosomal recessive type 20 (SPG20) [MIM: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.^[1]

Function

[SPG20_HUMAN] May be implicated in endosomal trafficking, or microtubule dynamics, or both.^[2] [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.^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH. SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet. 2002 Aug;31(4):347-8. Epub 2002 Jul 22. PMID:12134148 doi:10.1038/ng937
↑ Ciccarelli FD, Proukakis C, Patel H, Cross H, Azam S, Patton MA, Bork P, Crosby AH. The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. Genomics. 2003 Apr;81(4):437-41. PMID:12676568
↑ Bajorek M, Morita E, Skalicky JJ, Morham SG, Babst M, Sundquist WI. Biochemical analyses of human IST1 and its function in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1360-73. doi: 10.1091/mbc.E08-05-0475. Epub 2009, Jan 7. PMID:19129479 doi:http://dx.doi.org/10.1091/mbc.E08-05-0475
↑ Agromayor M, Carlton JG, Phelan JP, Matthews DR, Carlin LM, Ameer-Beg S, Bowers K, Martin-Serrano J. Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1374-87. doi: 10.1091/mbc.E08-05-0474. Epub 2009, Jan 7. PMID:19129480 doi:http://dx.doi.org/10.1091/mbc.E08-05-0474
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u7i"

@@ Line 3: / Line 3: @@
 <StructureSection load='4u7i' size='340' side='right' caption='[[4u7i]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u7i]] is a 2 chain structure. 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 [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>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u7e|4u7e]], [[4u7y|4u7y]]</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'>[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>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Guo, E Z]]
 [[Category: Xu, Z]]

4u7i

From Proteopedia

Revision as of 12:07, 6 November 2017

Structure of the complex of Spartin MIT and IST1 MIM

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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