4abm

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Template:STRUCTURE 4abm

Contents

Crystal Structure of CHMP4B hairpin

Template:ABSTRACT PUBMED 22406677

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]

About this Structure

4abm is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • 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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

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