8ei1: Difference between revisions

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'''Unreleased structure'''


The entry 8ei1 is ON HOLD  until Paper Publication
==Crystal structure of the N-terminal domain of CUL4B in complex with H316, a Helicon Polypeptide==
 
<StructureSection load='8ei1' size='340' side='right'caption='[[8ei1]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
Authors: Li, K., Tokareva, O.S., Thomson, T.M., Verdine, G.L., McGee, J.H.
== Structural highlights ==
 
<table><tr><td colspan='2'>[[8ei1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EI1 FirstGlance]. <br>
Description: Crystal structure of the N-terminal domain of CUL4B in complex with H316, a Helicon Polypeptide
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89&#8491;</td></tr>
[[Category: Unreleased Structures]]
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=WHL:N,N-(1,4-phenylene)diacetamide'>WHL</scene></td></tr>
[[Category: Tokareva, O.S]]
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ei1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ei1 OCA], [https://pdbe.org/8ei1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ei1 RCSB], [https://www.ebi.ac.uk/pdbsum/8ei1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ei1 ProSAT]</span></td></tr>
[[Category: Li, K]]
</table>
[[Category: Mcgee, J.H]]
== Disease ==
[[Category: Verdine, G.L]]
[https://www.uniprot.org/uniprot/CUL4B_HUMAN CUL4B_HUMAN] Defects in CUL4B are the cause of mental retardation, X-linked, syndromic, 15 (MRXS15) [MIM:[https://omim.org/entry/300354 300354]. A syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span.<ref>PMID:17273978</ref> <ref>PMID:20002452</ref> <ref>PMID:17236139</ref> <ref>PMID:19377476</ref>
[[Category: Thomson, T.M]]
== Function ==
[https://www.uniprot.org/uniprot/CUL4B_HUMAN CUL4B_HUMAN] Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8.<ref>PMID:14578910</ref> <ref>PMID:16322693</ref> <ref>PMID:16678110</ref> <ref>PMID:18593899</ref> <ref>PMID:18235224</ref> <ref>PMID:19801544</ref>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Li K]]
[[Category: McGee JH]]
[[Category: Thomson TM]]
[[Category: Tokareva OS]]
[[Category: Verdine GL]]

Latest revision as of 10:03, 25 October 2023

Crystal structure of the N-terminal domain of CUL4B in complex with H316, a Helicon PolypeptideCrystal structure of the N-terminal domain of CUL4B in complex with H316, a Helicon Polypeptide

Structural highlights

8ei1 is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.89Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CUL4B_HUMAN Defects in CUL4B are the cause of mental retardation, X-linked, syndromic, 15 (MRXS15) [MIM:300354. A syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span.[1] [2] [3] [4]

Function

CUL4B_HUMAN Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8.[5] [6] [7] [8] [9] [10]

References

  1. ↑ Zou Y, Liu Q, Chen B, Zhang X, Guo C, Zhou H, Li J, Gao G, Guo Y, Yan C, Wei J, Shao C, Gong Y. Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation. Am J Hum Genet. 2007 Mar;80(3):561-6. Epub 2007 Jan 25. PMID:17273978 doi:10.1086/512489
  2. ↑ Badura-Stronka M, Jamsheer A, Materna-Kiryluk A, Sowinska A, Kiryluk K, Budny B, Latos-Bielenska A. A novel nonsense mutation in CUL4B gene in three brothers with X-linked mental retardation syndrome. Clin Genet. 2010 Feb;77(2):141-4. doi: 10.1111/j.1399-0004.2009.01331.x. Epub, 2009 Dec 10. PMID:20002452 doi:10.1111/j.1399-0004.2009.01331.x
  3. ↑ Tarpey PS, Raymond FL, O'Meara S, Edkins S, Teague J, Butler A, Dicks E, Stevens C, Tofts C, Avis T, Barthorpe S, Buck G, Cole J, Gray K, Halliday K, Harrison R, Hills K, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Varian J, West S, Widaa S, Mallya U, Moon J, Luo Y, Holder S, Smithson SF, Hurst JA, Clayton-Smith J, Kerr B, Boyle J, Shaw M, Vandeleur L, Rodriguez J, Slaugh R, Easton DF, Wooster R, Bobrow M, Srivastava AK, Stevenson RE, Schwartz CE, Turner G, Gecz J, Futreal PA, Stratton MR, Partington M. Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor. Am J Hum Genet. 2007 Feb;80(2):345-52. Epub 2007 Jan 4. PMID:17236139 doi:10.1086/511134
  4. ↑ Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O'Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue Y, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia M, Richardson D, Shepherd R, Wooster R, Tejada MI, Martinez F, Carvill G, Goliath R, de Brouwer AP, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers HH, Abidi FE, Srivastava AK, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie JL, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton DF, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson RE, Bobrow M, Turner G, Schwartz CE, Gecz J, Raymond FL, Futreal PA, Stratton MR. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet. 2009 May;41(5):535-43. doi: 10.1038/ng.367. Epub 2009 Apr 19. PMID:19377476 doi:10.1038/ng.367
  5. ↑ Higa LA, Mihaylov IS, Banks DP, Zheng J, Zhang H. Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat Cell Biol. 2003 Nov;5(11):1008-15. Epub 2003 Oct 26. PMID:14578910 doi:10.1038/ncb1061
  6. ↑ Higa LA, Yang X, Zheng J, Banks D, Wu M, Ghosh P, Sun H, Zhang H. Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation. Cell Cycle. 2006 Jan;5(1):71-7. Epub 2006 Jan 21. PMID:16322693
  7. ↑ Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y. Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell. 2006 May 5;22(3):383-94. PMID:16678110 doi:S1097-2765(06)00230-9
  8. ↑ Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapic-Otrin V. The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A. Cancer Res. 2008 Jul 1;68(13):5014-22. PMID:18593899 doi:68/13/5014
  9. ↑ Ghosh P, Wu M, Zhang H, Sun H. mTORC1 signaling requires proteasomal function and the involvement of CUL4-DDB1 ubiquitin E3 ligase. Cell Cycle. 2008 Feb 1;7(3):373-81. Epub 2007 Nov 2. PMID:18235224
  10. ↑ Zou Y, Mi J, Cui J, Lu D, Zhang X, Guo C, Gao G, Liu Q, Chen B, Shao C, Gong Y. Characterization of nuclear localization signal in the N terminus of CUL4B and its essential role in cyclin E degradation and cell cycle progression. J Biol Chem. 2009 Nov 27;284(48):33320-32. doi: 10.1074/jbc.M109.050427. Epub, 2009 Oct 2. PMID:19801544 doi:10.1074/jbc.M109.050427

8ei1, resolution 2.89Å

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