Preliminary Crystallographic Studies of BRCA1 BRCT-ABRAXAS Complex

Overview

Journal Acta Crystallogr Sect F Struct Biol Cryst Commun

Date 2013 Dec 10

PMID 24316840

Citations 2

Authors

Dilip C Badgujar

Ulka Sawant

Lumbini Yadav

M V Hosur

Ashok K Varma

Affiliations

Soon will be listed here.

Abstract

The BRCA1 holoenzyme complex plays an important role in DNA damage repair. ABRAXAS is a newly discovered component of this complex and its C-terminal region directly binds to the BRCA1 BRCT domain. Single crystals of the BRCA1 BRCT-ABRAXAS complex grown by co-crystallization belonged to space group P4(1)2(1)2, with unit-cell parameters a = b = 187.18, c = 85.31 Å. Diffraction data were collected on the BM-14 beamline at the ESRF. Molecular-replacement calculations using Phaser led to three molecules in the asymmetric unit and a high solvent content of 76%.

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References

Yu X, Chini C, He M, Mer G, Chen J . The BRCT domain is a phospho-protein binding domain. Science. 2003; 302(5645):639-42. DOI: 10.1126/science.1088753. View

Wang B, Matsuoka S, Ballif B, Zhang D, Smogorzewska A, Gygi S . Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007; 316(5828):1194-8. PMC: 3573690. DOI: 10.1126/science.1139476. View

Campbell S, Edwards R, Glover J . Comparison of the structures and peptide binding specificities of the BRCT domains of MDC1 and BRCA1. Structure. 2010; 18(2):167-76. DOI: 10.1016/j.str.2009.12.008. View

Williams R, Chasman D, Hau D, Hui B, Lau A, Glover J . Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. J Biol Chem. 2003; 278(52):53007-16. DOI: 10.1074/jbc.M310182200. View

Solyom S, Aressy B, Pylkas K, Patterson-Fortin J, Hartikainen J, Kallioniemi A . Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions. Sci Transl Med. 2012; 4(122):122ra23. PMC: 3869525. DOI: 10.1126/scitranslmed.3003223. View

Shiozaki E, Gu L, Yan N, Shi Y . Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling. Mol Cell. 2004; 14(3):405-12. DOI: 10.1016/s1097-2765(04)00238-2. View

Battye T, Kontogiannis L, Johnson O, Powell H, Leslie A . iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):271-81. PMC: 3069742. DOI: 10.1107/S0907444910048675. View

Shao G, Patterson-Fortin J, Messick T, Feng D, Shanbhag N, Wang Y . MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks. Genes Dev. 2009; 23(6):740-54. PMC: 2661612. DOI: 10.1101/gad.1739609. View

Rodriguez M, Yu X, Chen J, Songyang Z . Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. J Biol Chem. 2003; 278(52):52914-8. DOI: 10.1074/jbc.C300407200. View

10.

Manke I, Lowery D, Nguyen A, Yaffe M . BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science. 2003; 302(5645):636-9. DOI: 10.1126/science.1088877. View

11.

Clapperton J, Manke I, Lowery D, Ho T, Haire L, Yaffe M . Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol. 2004; 11(6):512-8. DOI: 10.1038/nsmb775. View

12.

Varma A, Brown R, Birrane G, Ladias J . Structural basis for cell cycle checkpoint control by the BRCA1-CtIP complex. Biochemistry. 2005; 44(33):10941-6. DOI: 10.1021/bi0509651. View

13.

McCoy A, Grosse-Kunstleve R, Adams P, Winn M, Storoni L, Read R . Phaser crystallographic software. J Appl Crystallogr. 2009; 40(Pt 4):658-674. PMC: 2483472. DOI: 10.1107/S0021889807021206. View

14.

Matthews B . Solvent content of protein crystals. J Mol Biol. 1968; 33(2):491-7. DOI: 10.1016/0022-2836(68)90205-2. View