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| | ==The crystal structure of FANCM bound MHF complex== | | ==The crystal structure of FANCM bound MHF complex== |
| - | <StructureSection load='4drb' size='340' side='right' caption='[[4drb]], [[Resolution|resolution]] 2.63Å' scene=''> | + | <StructureSection load='4drb' size='340' side='right'caption='[[4drb]], [[Resolution|resolution]] 2.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4drb]] is a 15 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=4DRB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DRB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4drb]] is a 15 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=4DRB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DRB FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dra|4dra]]</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=4drb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4drb OCA], [https://pdbe.org/4drb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4drb RCSB], [https://www.ebi.ac.uk/pdbsum/4drb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4drb ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APITD1, CENPS, FAAP16, MHF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FANCM, KIAA1596 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), STRA13, CENPX, FAAP10, MHF2 ([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=4drb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4drb OCA], [http://pdbe.org/4drb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4drb RCSB], [http://www.ebi.ac.uk/pdbsum/4drb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4drb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CENPS_HUMAN CENPS_HUMAN]] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Required for optimal chromatin association of the FA core complex. Required for efficient damage-induced monoubiquitination and focus formation of FANCD2. Stabilizes FAAD24, FANCM and STRA13/CENPX in the FA core complex. Plays a role in DNA interstrand cross-linking (ICL) repair and in recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates induced by camptothecin. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.<ref>PMID:19620631</ref> <ref>PMID:22814378</ref> [REFERENCE:8] [[http://www.uniprot.org/uniprot/CENPX_HUMAN CENPX_HUMAN]] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation.<ref>PMID:19620631</ref> <ref>PMID:22814378</ref> [REFERENCE:6] [[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions.<ref>PMID:16116422</ref> <ref>PMID:16116434</ref> [REFERENCE:7][REFERENCE:8] | + | [[https://www.uniprot.org/uniprot/CENPS_HUMAN CENPS_HUMAN]] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Required for optimal chromatin association of the FA core complex. Required for efficient damage-induced monoubiquitination and focus formation of FANCD2. Stabilizes FAAD24, FANCM and STRA13/CENPX in the FA core complex. Plays a role in DNA interstrand cross-linking (ICL) repair and in recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates induced by camptothecin. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.<ref>PMID:19620631</ref> <ref>PMID:22814378</ref> [REFERENCE:8] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Centromere protein|Centromere protein]] | + | *[[Centromere protein 3D structure|Centromere protein 3D structure]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Niu, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Tao, Y]] | + | [[Category: Niu L]] |
| - | [[Category: Teng, M]] | + | [[Category: Tao Y]] |
| - | [[Category: Dna binding]] | + | [[Category: Teng M]] |
| - | [[Category: Dna binding complex]]
| + | |
| - | [[Category: Dna binding protein-protein binding complex]]
| + | |
| - | [[Category: Dna binding-protein binding complex]]
| + | |
| - | [[Category: Dna damage repair]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Histone fold]]
| + | |
| Structural highlights
Function
[CENPS_HUMAN] DNA-binding component of the FA core complex involved in DNA damage repair and genome maintenance. Required for optimal chromatin association of the FA core complex. Required for efficient damage-induced monoubiquitination and focus formation of FANCD2. Stabilizes FAAD24, FANCM and STRA13/CENPX in the FA core complex. Plays a role in DNA interstrand cross-linking (ICL) repair and in recovery of replication forks stalled by topoisomerase I-DNA cleavage intermediates induced by camptothecin. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. Component of the APITD1/CENPS complex that is essential for the stable assembly of the outer kinetochore. Plays an important role in mitotic progression and chromosome segregation. Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.[1] [2] [REFERENCE:8]
Publication Abstract from PubMed
Fanconi anaemia is a rare genetic disease characterized by chromosomal instability and cancer susceptibility. The Fanconi anaemia complementation group protein M (FANCM) forms an evolutionarily conserved DNA-processing complex with MHF1/MHF2 (histone-fold-containing proteins), which is essential for DNA repair in response to genotoxic stress. Here we present the crystal structures of the MHF1-MHF2 complex alone and bound to a fragment of FANCM (FANCM(661-800), designated FANCM-F). The structures show that MHF1 and MHF2 form a compact tetramer to which FANCM-F binds through a 'dual-V' shaped structure. FANCM-F and (MHF1-MHF2)(2) cooperate to constitute a new DNA-binding site that is coupled to the canonical L1L2 region. Perturbation of the MHF-FANCM-F structural plasticity changes the localization of FANCM in vivo. The MHF-FANCM interaction and its subcellular localization are altered by a disease-associated mutant of FANCM. These findings reveal the molecular basis of MHF-FANCM recognition and provide mechanistic insights into the pathway leading to Fanconi anaemia.
The structure of the FANCM-MHF complex reveals physical features for functional assembly.,Tao Y, Jin C, Li X, Qi S, Chu L, Niu L, Yao X, Teng M Nat Commun. 2012 Apr 17;3:782. doi: 10.1038/ncomms1779. PMID:22510687[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Amano M, Suzuki A, Hori T, Backer C, Okawa K, Cheeseman IM, Fukagawa T. The CENP-S complex is essential for the stable assembly of outer kinetochore structure. J Cell Biol. 2009 Jul 27;186(2):173-82. doi: 10.1083/jcb.200903100. Epub 2009 Jul, 20. PMID:19620631 doi:http://dx.doi.org/10.1083/jcb.200903100
- ↑ Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi:, 10.1073/pnas.1210303109. Epub 2012 Jul 18. PMID:22814378 doi:http://dx.doi.org/10.1073/pnas.1210303109
- ↑ Tao Y, Jin C, Li X, Qi S, Chu L, Niu L, Yao X, Teng M. The structure of the FANCM-MHF complex reveals physical features for functional assembly. Nat Commun. 2012 Apr 17;3:782. doi: 10.1038/ncomms1779. PMID:22510687 doi:10.1038/ncomms1779
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