The crystal structure of human interferon beta at 2.2-A resolution - PubMed (original) (raw)

Comparative Study

The crystal structure of human interferon beta at 2.2-A resolution

M Karpusas et al. Proc Natl Acad Sci U S A. 1997.

Abstract

Type I interferons (IFNs) are helical cytokines that have diverse biological activities despite the fact that they appear to interact with the same receptor system. To achieve a better understanding of the structural basis for the different activities of alpha and beta IFNs, we have determined the crystal structure of glycosylated human IFN-beta at 2.2-A resolution by molecular replacement. The molecule adopts a fold similar to that of the previously determined structures of murine IFN-beta and human IFN-alpha2b but displays several distinct structural features. Like human IFN-alpha2b, human IFN-beta contains a zinc-binding site at the interface of the two molecules in the asymmetric unit, raising the question of functional relevance for IFN-beta dimers. However, unlike the human IFN-alpha2b dimer, in which homologous surfaces form the interface, human IFN-beta dimerizes with contact surfaces from opposite sides of the molecule. The relevance of the structure to the effects of point mutations in IFN-beta at specific exposed residues is discussed. A potential role of ligand-ligand interactions in the conformational assembly of IFN receptor components is discussed.

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Figures

Figure 1

Figure 1

Representative region of a simulated annealing omit map displayed in stereo for residues 61–67 of molecule A and contoured at 1σ. The figure was made with the program

quanta

.

Figure 2

Figure 2

Schematic representation of the crystallographic dimer of huIFN-β. The modeled portion of the carbohydrates and part of the zinc-binding site are also shown. The sphere corresponds to the zinc ion. Helices and N and C termini are labeled. The AB loop is colored green. The figure was made with the program

molscript

(44).

Figure 3

Figure 3

Superposition of Cα traces of molecules A (in green), B (blue), and muIFN-β (red) in stereo. The figure was made with the program

molscript

(44).

Figure 4

Figure 4

Ribbon diagram of huIFN-β Cα backbone with side chains of residues known to be important for activity. The yellow spheres represent the sulfur atoms of the disulfide bridge. The ribbon is colored red at positions of the alanine-scanning mutagenesis cited in ref. . Orange spheres correspond to Cα atoms of residues homologous to those of IFN-α that are important for activity. Part of the zinc-binding site is also shown. The figure was made with the program

molscript

(44).

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