4abm

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Revision as of 20:29, 5 August 2016

Crystal Structure of CHMP4B hairpin

Structural highlights

4abm is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CHM4B_HUMAN] Defects in CHMP4B are the cause of cataract posterior polar type 3 (CTPP3) [MIM:605387]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.^[1]

Function

[CHM4B_HUMAN] Probable core 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. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release.^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Endosomal sorting complexes required for transport (ESCRTs) regulate diverse processes ranging from receptor sorting at endosomes to distinct steps in cell division and budding of some enveloped viruses. Common to all processes is the membrane recruitment of ESCRT-III that leads to membrane fission. Here, we show that CC2D1A is a novel regulator of ESCRT-III CHMP4B function. We demonstrate that CHMP4B interacts directly with CC2D1A and CC2D1B with nanomolar affinity by forming a 1:1 complex. Deletion mapping revealed a minimal CC2D1A-CHMP4B binding construct, which includes a short linear sequence within the third DM14 domain of CC2D1A. The CC2D1A binding site on CHMP4B was mapped to the N-terminal helical hairpin. Based on a crystal structure of the CHMP4B helical hairpin, two surface patches were identified that interfere with CC2D1A interaction as determined by surface plasmon resonance. Introducing these mutations into a C-terminal truncation of CHMP4B that exerts a potent dominant negative effect on human immunodeficiency virus type 1 budding revealed that one of the mutants lost this effect completely. This suggests that the identified CC2D1A binding surface might be required for CHMP4B polymerization, which is consistent with the finding that CC2D1A binding to CHMP4B prevents CHMP4B polymerization in vitro. Thus, CC2D1A might act as a negative regulator of CHMP4B function.

CC2D1A Is a Regulator of ESCRT-III CHMP4B.,Martinelli N, Hartlieb B, Usami Y, Sabin C, Dordor A, Miguet N, Avilov SV, Ribeiro EA Jr, Gottlinger H, Weissenhorn W J Mol Biol. 2012 May 25;419(1-2):75-88. Epub 2012 Mar 8. PMID:22406677^[7]

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

References

↑ Shiels A, Bennett TM, Knopf HL, Yamada K, Yoshiura K, Niikawa N, Shim S, Hanson PI. CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q. Am J Hum Genet. 2007 Sep;81(3):596-606. Epub 2007 Jul 27. PMID:17701905 doi:S0002-9297(07)61356-1
↑ Katoh K, Shibata H, Suzuki H, Nara A, Ishidoh K, Kominami E, Yoshimori T, Maki M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J Biol Chem. 2003 Oct 3;278(40):39104-13. Epub 2003 Jul 14. PMID:12860994 doi:10.1074/jbc.M301604200
↑ Strack B, Calistri A, Craig S, Popova E, Gottlinger HG. AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell. 2003 Sep 19;114(6):689-99. PMID:14505569
↑ von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Krausslich HG, Kaplan J, Morham SG, Sundquist WI. The protein network of HIV budding. Cell. 2003 Sep 19;114(6):701-13. PMID:14505570
↑ Martin-Serrano J, Yarovoy A, Perez-Caballero D, Bieniasz PD. Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12414-9. Epub 2003 Sep 30. PMID:14519844 doi:10.1073/pnas.2133846100
↑ Hanson PI, Roth R, Lin Y, Heuser JE. Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. J Cell Biol. 2008 Jan 28;180(2):389-402. Epub 2008 Jan 21. PMID:18209100 doi:jcb.200707031
↑ Martinelli N, Hartlieb B, Usami Y, Sabin C, Dordor A, Miguet N, Avilov SV, Ribeiro EA Jr, Gottlinger H, Weissenhorn W. CC2D1A Is a Regulator of ESCRT-III CHMP4B. J Mol Biol. 2012 May 25;419(1-2):75-88. Epub 2012 Mar 8. PMID:22406677 doi:10.1016/j.jmb.2012.02.044

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/4abm"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of CHMP4B hairpin==
 <StructureSection load='4abm' size='340' side='right' caption='[[4abm]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4abm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ABM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ABM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4abm]] 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=4ABM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ABM FirstGlance]. <br>
-</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=4abm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4abm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4abm RCSB], [http://www.ebi.ac.uk/pdbsum/4abm PDBsum]</span></td></tr>
+</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=4abm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4abm OCA], [http://pdbe.org/4abm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4abm RCSB], [http://www.ebi.ac.uk/pdbsum/4abm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4abm ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4abm" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Dordor, A]]
 [[Category: Gottlinger, H]]

4abm

From Proteopedia

Revision as of 20:29, 5 August 2016

Crystal Structure of CHMP4B hairpin

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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