1imo
NMR STRUCTURE OF HUMAN DNA LIGASE IIIALPHA BRCT DOMAIN
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OverviewOverview
BRCT (BRCA1 carboxyl terminus) domains are found in a number of DNA repair, enzymes and cell cycle regulators and are believed to mediate important, protein-protein interactions. The DNA ligase IIIalpha BRCT domain partners, with the distal BRCT domain of the DNA repair protein XRCC1 (X1BRCTb) in, the DNA base excision repair (BER) pathway. To elucidate the mechanisms by, which these two domains can interact, we have determined the solution, structure of human ligase IIIalpha BRCT (L3[86], residues 837-922). The, structure of L3[86] consists of a beta2beta1beta3beta4 parallel sheet with, a two-alpha-helix bundle packed against one face of the sheet. This fold, is conserved in several proteins having a wide range of activities, including X1BRCTb [Zhang, X. D., et al. (1998) EMBO J. 17, 6404-6411]., L3[86] exists as a dimer in solution, but an insufficient number of NOE, restraints precluded the determination of the homodimer structure., However, 13C isotope-filtered and hydrogen-deuterium exchange experiments, indicate that the N-terminus, alpha1, the alpha1-beta2 loop, and the three, residues following alpha2 are involved in forming the dimer interface, as, similarly observed in the structure of X1BRCTb. NOE and dynamic data, indicate that several residues (837-844) in the N-terminal region appear, to interconvert between helix and random coil conformations. Further, studies of other BRCT domains and of their complexes are needed to address, how these proteins interact with one another, and to shed light on how, mutations can lead to disruption of function and ultimately disease.
About this StructureAbout this Structure
1IMO is a Single protein structure of sequence from Homo sapiens. Active as DNA ligase (ATP), with EC number 6.5.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Solution structure and backbone dynamics of the human DNA ligase IIIalpha BRCT domain., Krishnan VV, Thornton KH, Thelen MP, Cosman M, Biochemistry. 2001 Nov 6;40(44):13158-66. PMID:11683624
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