PDBsum entry 1nfi

Complex (transcription reg/ank repeat)

PDB id: 1nfi

Contents

Protein chains

295 a.a. *

107 a.a. *

213 a.a. *

Waters ×71

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of an ikappabalpha/nf-Kappab complex.

Authors

M.D.Jacobs, S.C.Harrison.

Ref.

Cell, 1998, 95, 749-758. [DOI no: 10.1016/S0092-8674(00)81698-0]

PubMed id

9865693

Abstract

The inhibitory protein, IkappaBalpha, sequesters the transcription factor, NF-kappaB, as an inactive complex in the cytoplasm. The structure of the IkappaBalpha ankyrin repeat domain, bound to a partially truncated NF-kappaB heterodimer (p50/ p65), has been determined by X-ray crystallography at 2.7 A resolution. It shows a stack of six IkappaBalpha ankyrin repeats facing the C-terminal domains of the NF-kappaB Rel homology regions. Contacts occur in discontinuous patches, suggesting a combinatorial quality for ankyrin repeat specificity. The first two repeats cover an alpha helically ordered segment containing the p65 nuclear localization signal. The position of the sixth ankyrin repeat shows that full-length IkappaBalpha will occlude the NF-kappaB DNA-binding cleft. The orientation of IkappaBalpha in the complex places its N- and C-terminal regions in appropriate locations for their known regulatory functions.

Figure 4.
Figure 4. Contacts between NF-κB and IκBα(a) The backbone of IκBα is shown as an orange strand against the van der Waals contact surface of NF-κB. The surface is colored dark blue where the center of an atom of IκBα is within 3.8 Å of an atom of NF-κB, and graded from light blue to white for distances up to 4.5 Å. This figure is related by a 180° rotation relative to the view in Figure 1B. The thin strip of continuity between the p50 contact (left) and the p65 contact (right) is the conserved salt-bridge network shown in Figure 5B.(b) The backbones of the dimerization domains of NF-κB are shown as orange strands against the van der Waals contact surface of IκBα. This view is in the same orientation as Figure 1B. Note how the fingers of IκBα project forward toward the edge of the p50 RHR-c.(c) Residues of IκBα where side chains make contacts with NF-κB are shown in color on a space-filling representation of the ankyrin repeat stack. The orientation of the model is the same as in Figure 1B and Figure 4B. Residues contacting the p50 RHR-c are in red; those contacting p65 RHR-c are in dark blue; those contacting the p65 NLS and the segment C-terminal to it are in light blue. These residues are also indicated by colored boxes in Figure 3A. (a) and (b) were made using the program GRASP ( [45]), and (c), using the program RIBBONS ( [13]).

Figure 6.
Figure 6. Diagram of the IκB/NF-κB Complex, Showing Additional Interactions and Relative Positions of Domains Not Included in the Crystal StructureSpace-filling representations of the ankyrin domain of IκBα and of the RHRs of p65 and p50 are shown, with strands to represent N- or C-terminal extensions. The C-terminal extension of p65 includes segments likely to interact with the transcription machinery. The C terminus of p50 following the NLS is a glycine-rich tail. In p105, this tail connects to an IκB domain. The figure shows that this connection can be a simple loop. The N-terminal 69 residues of IκBα include the sites for phosphorylation and ubiquitination as well as residues thought to mask the p50 NLS. The C-terminal extension of IκBα occludes the DNA-binding site; it contains a proline, glutamic-acid, serine, and threonine-rich segment (PEST domain), which regulates basal turnover ([59]). The color scheme conforms to Figure 1. Features with labels in colored boxes are parts of the complex not present or not ordered in the crystal structure. The p50 RHR-n has been modeled in an orientation, relative to p50 RHR-c, similar to the orientation of p65 RHR-n relative to p65 RHR-c in the structure. Both of the RHR N-terminal domains may actually adopt a variety of orientations, due to the flexibility of the RHR linker. Figures made with the program RIBBONS ( [13]).

The above figures are reprinted by permission from Cell Press: Cell (1998, 95, 749-758) copyright 1998.