PDBsum entry 1k1a

Transcription

PDB id: 1k1a

Contents

Protein chain

228 a.a. *

Waters ×195

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of the ankyrin repeat domain of bcl-3: a unique member of the ikappab protein family.

Authors

F.Michel, M.Soler-Lopez, C.Petosa, P.Cramer, U.Siebenlist, C.W.Müller.

Ref.

EMBO J, 2001, 20, 6180-6190. [DOI no: 10.1093/emboj/20.22.6180]

PubMed id

11707390

Abstract

IkappaB proteins associate with the transcription factor NF-kappaB via their ankyrin repeat domain. Bcl-3 is an unusual IkappaB protein because it is primarily nucleoplasmic and can lead to enhanced NF-kappaB-dependent transcription, unlike the prototypical IkappaB protein IkappaBalpha, which inhibits NF-kappaB activity by retaining it in the cytoplasm. Here we report the 1.9 A crystal structure of the ankyrin repeat domain of human Bcl-3 and compare it with that of IkappaBalpha bound to NF-kappaB. The two structures are highly similar over the central ankyrin repeats but differ in the N-terminal repeat and at the C-terminus, where Bcl-3 contains a seventh repeat in place of the acidic PEST region of IkappaBalpha. Differences between the two structures suggest why Bcl-3 differs from IkappaBalpha in selectivity towards various NF-kappaB species, why Bcl-3 but not IkappaBalpha can associate with its NF-kappaB partner bound to DNA, and why two molecules of Bcl-3 but only one of IkappaBalpha can bind to its NF-kappaB partner. Comparison of the two structures thus provides an insight into the functional diversity of IkappaB proteins.

Figure 4.
Figure 4 Comparison of Bcl-3 and I B molecular surfaces. The structures of I B (A, B, E and F) and Bcl-3 (C, D, G and H) are shown in equivalent orientations. The view of (A) -(D) is orthogonal to that of (E) -(H), which is approximately that of Figure 1B (i.e. with -hairpins on the left and 2 helices on the right.) (A, D, E and H) Comparison of electrostatic surface potentials. Regions of negative and positive potential are shown in red and blue, respectively. The basic patch at the bottom of Bcl-3 is formed by arginine residues 311, 318, 322, 342, 344, 345 and 351. The corresponding surface of I B is formed by the acidic PEST region. (B, C, F and G) Conservation of the NF- B contact surface. The C-terminal domains of p50 (blue) and p65 (green) are represented as ribbons bound to the surface of I B and, to facilitate comparison, to that of Bcl-3. In (B) and (F), regions of the I B surface within 4.5 Å of the p50 and p65 RHR-c domains are colored magenta. In (C) and (G), surface-exposed residues, which are identically conserved between Bcl-3 and I B , are shown in yellow. The asterisks and triangles indicate regions of the I B surface in contact with NF- B that are composed of residues poorly conserved in Bcl-3. This figure was prepared using GRASP (Nicholls et al., 1991).

Figure 6.
Figure 6 Hypothetical model of Bcl-3 bound to a DNA-bound p50 homodimer. The model was constructed based on the structure of the I B -NF B complex, by structurally aligning Bcl-3 (yellow) onto I B (red) and a DNA-bound p50 homodimer (green and blue; Müller et al., 1995) onto the p50 -p65 heterodimer (not shown, although it is nearly identical to the p50 homodimer, where the green monomer corresponds to the p65 subunit). A 30-base pair stretch of ideal B-form DNA was then superimposed onto the shorter duplex present in the p50 -DNA crystal structure. (A) Side view showing that sufficient space is available next to the DNA to accommodate ANK repeat 7 of Bcl-3 but not the PEST region of I B . (B) View showing that the C-terminal domains of I B and Bcl-3 are positioned on opposite sides of the ARD. The view is that of (A) rotated by 110° about the vertical axis.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 6180-6190) copyright 2001.