PDBsum entry 1jnx

Gene regulation

PDB id: 1jnx

Contents

Protein chain

207 a.a. *

Metals

_NI

Waters ×115

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of the brct repeat region from the breast cancer-Associated protein brca1.

Authors

R.S.Williams, R.Green, J.N.Glover.

Ref.

Nat Struct Biol, 2001, 8, 838-842. [DOI no: 10.1038/nsb1001-838]

PubMed id

11573086

Abstract

The C-terminal BRCT region of BRCA1 is essential for its DNA repair, transcriptional regulation and tumor suppressor functions. Here we determine the crystal structure of the BRCT domain of human BRCA1 at 2.5 A resolution. The domain contains two BRCT repeats that adopt similar structures and are packed together in a head-to-tail arrangement. Cancer-causing missense mutations occur at the interface between the two repeats and destabilize the structure. The manner by which the two BRCT repeats interact in BRCA1 may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage. The structure provides a basis to predict the structural consequences of uncharacterized BRCA1 mutations.

Figure 2.
Figure 2. The structure of the dual repeat BRCT domain of BRCA1. a, A ribbons representation of the BRCT domain. The secondary structure elements in the C-terminal BRCT repeat are labeled 'prime' to distinguish them from the corresponding secondary structure elements in the N-terminal repeat. b, C backbone trace of the BRCA1 BRCT domain. The N-terminal BRCT repeat is colored turquoise; the C-terminal repeat, gold; and the inter-repeat linker, gray. The view is rotated 90° clockwise from the view shown in (a). c, MAD-phased electron density at 2.9 Å resolution and contoured at 1.0 is displayed for the inter-BRCT repeat interface. d, A stereo view of a structural alignment of the N- and C-terminal BRCA1 BRCT repeats and the C-terminal BRCT repeat from XRCC1 (ref. 10). Least squares alignments were produced using O23.

Figure 3.
Figure 3. The packing of BRCT repeats. a, Stereo view of the interaction of three helices to form the core of the BRCT repeat interface. b, An electrostatic surface representation of the C-terminal BRCT repeat is displayed with a worm representation of 2 from the N-terminal repeat. c, An electrostatic surface representation of the N-terminal repeat is shown with a worm representation of 1' and 3' from the C-terminal repeat. In (a -c), the N-terminal repeat is colored turquoise; the C-terminal repeat, gold; and residues that cause cancer when mutated, red. d, An amino acid sequence alignment of the regions of BRCA1, 53BP1 and RAD9 that are predicted to form BRCT -BRCT interfaces. Residues that constitute this interface in BRCA1, as well as conserved residues in h53BP1 and S. cerevisiae RAD9, are colored green. Residues where cancer-causing missense mutations have been identified are boxed in red.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 838-842) copyright 2001.