Abstract
The breast cancer susceptibility protein 1 (BRCA1) plays a central role in the suppression of human breast and ovarian cancer. Germ line mutations of the BRCA1 gene are responsible for the hereditary breast and ovarian cancer (HBOC) syndrome. Here were report 1H, 13C, and 15N resonance assignments for the intrinsically disordered BRCA1 fragment 219–504, which contains important interaction sites for the proto-oncogenic transcription factor MYC as well as for p53. A nuclear magnetic resonance assignment was achieved at 18.8 T magnetic field strength using a 5D HN(CA)CONH experiment and its associated 4D H(NCA)CONH and 4D (H)N(CA)CONH experiments. 13Cα and 13Cβ assignments were obtained using a 5D HabCabCONH experiment. With this strategy, 90% of 1H/15N backbone pairs could be assigned. Similarly, 264 C’ resonances were assigned corresponding to 86% of the total number of C’ atoms. In addition, 252 Cβ resonances (i.e. 85%) were assigned, together with 461 attached Hβ nuclei, as well as 264 (i.e. 86%) Cα resonances, together with 275 attached Hα nuclei.
Highlights
The breast cancer susceptibility protein 1 (BRCA1) is an important factor for human breast and ovarian cancer suppression.(Narod and Foulkes 2004) germ line mutations of the BRCA1 gene have been linked to the hereditary breast and ovarian cancer (HBOC) syndrome in multiple
The full-length BRCA1 gene product consists of a stably folded N-terminal RING-domain and two C-terminal BRCT domains connected by a ∼1550 amino acid long intrinsically disordered region (IDR). (Mark et al 2005) We investigated a construct that consists of residues 219–504 belonging to the central linker domain
Product encoded by exon 11, and includes the majority of residues belonging to the reported MYC binding site(s) (Wang et al 1998). This BRCA1 domain contains 11 aromatic amino acids, which is atypical for IDRs
Summary
The breast cancer susceptibility protein 1 (BRCA1) is an important factor for human breast and ovarian cancer suppression.(Narod and Foulkes 2004) germ line mutations of the BRCA1 gene have been linked to the hereditary breast and ovarian cancer (HBOC) syndrome in multiple. Keywords BRCA1 · NMR · Chemical Shift Assignment · IDP · 4D and 5D NMR The full-length BRCA1 gene product consists of a stably folded N-terminal RING-domain (residues 1-103) and two C-terminal BRCT domains (residues 1646–1863) connected by a ∼1550 amino acid long intrinsically disordered region (IDR).
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