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4m6w

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Revision as of 09:02, 17 June 2015

Crystal structure of the C-terminal segment of FANCM in complex with FAAP24

Structural highlights

4m6w 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.
Ligands:
Gene:	FANCM, KIAA1596 (HUMAN), FAAP24, C19orf40 (HUMAN)
Activity:	RNA helicase, with EC number 3.6.4.13
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[FANCM_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.

Function

[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.^[1] ^[2] [REFERENCE:7][REFERENCE:8] [FAP24_HUMAN] Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA.

Publication Abstract from PubMed

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair.

Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair.,Yang H, Zhang T, Tao Y, Wang F, Tong L, Ding J Nucleic Acids Res. 2013 Sep 3. PMID:24003026^[3]

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

References

↑ Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005 Sep;37(9):958-63. Epub 2005 Aug 21. PMID:16116422 doi:ng1626
↑ Mosedale G, Niedzwiedz W, Alpi A, Perrina F, Pereira-Leal JB, Johnson M, Langevin F, Pace P, Patel KJ. The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway. Nat Struct Mol Biol. 2005 Sep;12(9):763-71. Epub 2005 Aug 21. PMID:16116434 doi:10.1038/nsmb981
↑ Yang H, Zhang T, Tao Y, Wang F, Tong L, Ding J. Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair. Nucleic Acids Res. 2013 Sep 3. PMID:24003026 doi:10.1093/nar/gkt788

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/4m6w"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4m6w|  PDB=4m6w  |  SCENE=  }}
+==Crystal structure of the C-terminal segment of FANCM in complex with FAAP24==
-===Crystal structure of the C-terminal segment of FANCM in complex with FAAP24===
+<StructureSection load='4m6w' size='340' side='right' caption='[[4m6w]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
-{{ABSTRACT_PUBMED_24003026}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4m6w]] 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=4M6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M6W FirstGlance]. <br>
-==Disease==
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FANCM, KIAA1596 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FAAP24, C19orf40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></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=4m6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m6w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m6w RCSB], [http://www.ebi.ac.uk/pdbsum/4m6w PDBsum]</span></td></tr>
+</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/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] [[http://www.uniprot.org/uniprot/FAP24_HUMAN FAP24_HUMAN]] Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair.
-==About this Structure==
+Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair.,Yang H, Zhang T, Tao Y, Wang F, Tong L, Ding J Nucleic Acids Res. 2013 Sep 3. PMID:24003026<ref>PMID:24003026</ref>
-[[4m6w]] is a 2 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=4M6W OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:024003026</ref><references group="xtra"/><references/>
+</div>
-[[Category: Homo sapiens]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
 [[Category: RNA helicase]]
-[[Category: Ding, J.]]
+[[Category: Ding, J]]
-[[Category: Tong, L.]]
+[[Category: Tong, L]]
-[[Category: Yang, H.]]
+[[Category: Yang, H]]
-[[Category: Zhang, T.]]
+[[Category: Zhang, T]]
 [[Category: Dna binding protein]]
 [[Category: Dna repair]]

4m6w

From Proteopedia

Revision as of 09:02, 17 June 2015

Crystal structure of the C-terminal segment of FANCM in complex with FAAP24

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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