7da1

Crystal structure of the chicken MHF complexCrystal structure of the chicken MHF complex

Structural highlights 7da1 is a 4 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.01Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CENPS_CHICK DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:20347428). In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM. In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks. In complex with CENPT, CENPW and CENPX (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression (PubMed:19620631). As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure. DNA-binding function is fulfilled in the presence of CENPX, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own (By similarity).[UniProtKB:Q8N2Z9] Publication Abstract from PubMed FANCM is involved in eukaryotic DNA-damage recognition and activates the Fanconi anemia (FA) pathway through complex formation. MHF is one of the FANCM-associating components and contains a histone-fold DNA-binding domain. Loss of the FANCM-MHF interaction compromises the activation of the FA pathway, resulting in chromosomal instability. Thus, formation of the FANCM-MHF complex is important for function, but its nature largely remains elusive. Here, the aim was to reveal the molecular and structural basis for the stability of the FANCM-MHF complex. A recombinant tripartite complex containing chicken FANCM (MHF interaction region), MHF1 and MHF2 was expressed and purified. The purified tripartite complex was crystallized under various conditions and three different crystals were obtained from similar crystallization conditions. Unexpectedly, structure determination revealed that one of the crystals contained the FANCM-MHF complex but that the other two contained the MHF complex without FANCM. How FANCM dissociates from MHF was further investigated and it was found that the presence of 2-methyl-2,4-pentanediol (MPD) and an oxidative environment may have promoted its release. However, under these conditions MHF retained its complexed form. FANCM-MHF interaction involves a mixture of hydrophobic/hydrophilic interactions, and chicken FANCM contains several nonconserved cysteines within this region which may lead to aggregation with other FANCM-MHF molecules. These results indicate an unexpected nature of the FANCM-MHF complex and the data can be used to improve the stability of the complex for biochemical and structural analyses. Structural analysis of the chicken FANCM-MHF complex and its stability.,Ito S, Nishino T Acta Crystallogr F Struct Biol Commun. 2021 Jan 1;77(Pt 1):1-7. doi: , 10.1107/S2053230X20016003. Epub 2021 Jan 1. PMID:33439149 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Centromere protein 3D structure

spinqualitylabelsall models 7da1, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image