title: Structural basis to characterise transactivation domain of BRCA1.
abstract: Familial inheritance of breast and ovarian cancer is attributed to mutations discovered in functional domains of BRCA1 gene. BRCA1 is a multifunctional protein responsible for maintaining the genomic integrity and has transcriptional regulatory function encoded in its C-terminal region. The different amino-terminal e extensions to BRCA1 BRCT domain are responsible for transcription activation. However, only BRCA1 BRCT (1649-1859) amino acids have been explored for its structural characteristics. Noting the importance of extended region to the N-terminus of BRCT different regions of BRCA1 which demonstrates maximum transactivation activity has been explored for their structure and functional activity. Secondary and tertiary structural analysis revealed a limited alpha-helical content with well-folded tertiary structure. In silico tools were used to corroborate the in vitro results. Amino acids composition and sequence analysis display a propensity for intrinsic disorder and coiled-coil formation in BRCA1 (1396-1863) (BRCA1-TAD). The results presented in this paper suggest the extreme flexibility in coiled-coil motif might be an important requirement in the establishment of protein-protein interaction networks for BRCA1.
authors.affiliation: a Advanced Centre for Treatment , Research and Education in Cancer , Kharghar, Navi-Mumbai , Maharashtra 410210 , India.
authors.forename: Lumbini R
authors.initials: LR
authors.lastname: Yadav
authors.affiliation: a Advanced Centre for Treatment , Research and Education in Cancer , Kharghar, Navi-Mumbai , Maharashtra 410210 , India.
authors.forename: Mahamaya N
authors.initials: MN
authors.lastname: Biswal
authors.affiliation: a Advanced Centre for Treatment , Research and Education in Cancer , Kharghar, Navi-Mumbai , Maharashtra 410210 , India.
authors.forename: M V
authors.initials: MV
authors.lastname: Hosur
authors.affiliation: b Department of Biotechnology , Mizoram University (A Central University) , Aizawl 796 004 , Mizoram , India.
authors.forename: Nachimuthu Senthil
authors.initials: NS
authors.lastname: Kumar
authors.affiliation: a Advanced Centre for Treatment , Research and Education in Cancer , Kharghar, Navi-Mumbai , Maharashtra 410210 , India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Varma
mesh_terms: D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
chemical_list: D019313:BRCA1 Protein; D011994:Recombinant Proteins
keywords: BRCA1; secondary and tertiary structure; transactivation domain