Three-dimensional crystal structure of recombinant murine interferon-beta.

Senda, Toshiya; Shimazu, Tsuneo; Matsuda, Susumu; Kawano, Genji; Shimizu, Hirohiko M.; Nakamura, Kazuo; Mitsui, Yukio

doi:10.1002/j.1460-2075.1992.tb05396.x

Cited by 126 publications

(49 citation statements)

References 68 publications

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“…Proteins in this family for which 3-dimensional structures are available include interleukin-2 [19] (IL2), interleukin-4 [20] (IL-4), granulocyte-macrophage colony-stimulating factor [21] (GMCSF), macrophage colony-stimulating factor [22] (M-CSF), granulocyte colony-stimulating factor [23] (G-CSF), growth hormone [24] (GH), and interferon-fl [25] (IFN-fl). Division into subclasses based on structural similarities beyond the 4-helix bundle places IL-2, IL4, GM-CSF and M-CSF into the 'short-chain' subclass, G-CSF and GH in the 'long-chain' subclass, and IFN-fl in the 'interferon-like' subclass [18].…”

Section: Resultsmentioning

confidence: 99%

Threading analysis suggests that the obese gene product may be a helical cytokine

1995

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The ob gene encodes a protein that, in mutant form, is associated with obesity and type II diabetes in mice. Sequence analysis has revealed no similarities to other proteins, however, and no clues as to possible functions. The possibility nonetheless remains that ob is functionally or ancestrally related to other proteins, whose sequences are divergent to the point that only a comparison of three-dimensional structures might detect relationship. To explore this possibility, we conduct a 'threading' search of a 3-dimensional structure database, to determine whether the ob protein might adopt a fold similar to any known structure. This search reveals that the ob sequence is compatible, at a significance level of P < 0.05, with structures from the family of helical cytokines that includes interleukin-2 and growth hormone. A structural model of ob based upon these results is physically and biologically plausible and leads to testable predictions, including the prediction that ob may activate the JAK-STAT pathway, via binding to a receptor resembling those of the cytokine family.

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Section: Resultsmentioning

confidence: 99%

Threading analysis suggests that the obese gene product may be a helical cytokine

1995

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“…2C,D). The novel helical segment identified on loop CD of the updated MuIFNP crystal structure (Senda & Mitsui, 1994) might possibly correct this misfolded region of loop CD, which can be verified when the coordinates for the new MuIFNP structure are available.…”

Section: Modeling Of the Interferonsmentioning

confidence: 90%

Homology model of human interferon‐α8 and its receptor complex

Seto¹,

Harkins²,

Adler³

et al. 1995

Protein Science

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Human interferond (HuIFNa8), a type I interferon (IFN), is a cytokine belonging to the hematopoietic superfamily that includes human growth hormone (HGH). Recent data identified two human type I IFN receptor components. One component (p40) was purified from human urine by its ability to bind to immobilized type I IFN. A second receptor component (IFNAR), consisting of two cytokine receptor-like domains (D200 and D200'), was identified by expression cloning. Murine cells transfected with a gene encoding this protein were able to produce an antiviral response to human IFNa8. Both of these receptor proteins have been identified as members of the immunoglobulin superfamily of which H G H receptor is a member. The cytokine receptor-like structural motifs present in p40 and IFNAR were modeled based on the HGH receptor X-ray structure. Models of the complexes of HuIFNa8 with the receptor subunits were built by superpositioning the conserved C a backbone of the HuIFNa8 and receptor subunit models with HGH and its receptor complex. The HuIFNa8 model was constructed from the Ca coordinates of murine interferon-p crystal structure. Electrostatic potentials and hydrophobic interactions appear to favor the model of HuIFNa8 interacting with p40 at site 1 and the D200' domain of IFNAR at site 2 because there are regions of complementary electrostatic potential and hydrophobic interactions at both of the proposed binding interfaces. Some of the predicted receptor binding residues within HuIFNa8 correspond to functionally important residues determined previously for human IFNal, IFNa2, and IFNa4 subtypes by site-directed mutagenesis studies. The models predict regions of interaction between HuIFNa8 and each of the receptor proteins, and provide insights into interactions between other type I IFNs (IFN-a subtypes and IFN-p) and their respective receptor components.

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“…C: Recombinant human GM-CSF at 2.4 A resolution (Diederichs-et al, 1991) D: Recombinant human IL-5 at 2.4 A resolution (Milburn et al,!993). E Recombinant murine interferon P at 2.2 A resolution (Senda et al, 1992). F: Recombinant human 1L-10 at 1.8 A resolution (Zdanov et al, 1995).…”

Section: Two Models For Oligomer Evolutionmentioning

confidence: 99%

3D domain swapping: A mechanism for oligomer assembly

1995

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Abstract3D domain swapping is a mechanism for forming oligomeric proteins from their monomers. In 3D domain swapping, one domain of a monomeric protein is replaced by the same domain from an identical protein chain. The result is an intertwined dimer or higher oligomer, with one domain of each subunit replaced by the identical domain from another subunit. The swapped "domain" can be as large as an entire tertiary globular domain, or as small as an a-helix or a strand of a P-sheet. Examples of 3D domain swapping are reviewed that suggest domain swapping can serve as a mechanism for functional interconversion between monomers and oligomers, and that domain swapping may serve as a mechanism for evolution of some oligomeric proteins. Domain-swapped proteins present examples of a single protein chain folding into two distinct structures.Keywords: aggregation; complementation; oligomer evolution; protein dimerization Since Svedberg's discovery of functional molecules composed of two or more identical protein chains, much effort has been expended in studying their metabolic regulation (Monod et al., 1965;Koshland et al., 1966) and their assembly and disassembly (Kikuchi & King, 1975;Caspar, 1980;Jaenicke, 1995).Despite this progress, understanding the assembly of oligomeric proteins from monomers remains a challenge. A common observation is that disassembly of an oligomeric protein into its monomeric subunits is accompanied by irreversible unfolding and aggregation. This observation is often interpreted in terms of exposing apolar patches on the monomer surface that are covered in the oligomer, thereby providing binding energy from a hydrophobic interaction. Thus, the question remains of how the oligomer could have been assembled in the first place. We propose an answer to this question for some oligomers based on a mode of association that we have noticed in several proteins of Reprint requests to: David Eisenberg, Molecular Biology Institute, Department of Chemistry and Biochemistry, and UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, University of California-Los Angeles, Los Angeles, California 90095-1570; e-mail: david@pauling.rnbi.ucla.edu.Abbreviations: BS-RNase, bovine seminal ribonuclease; DT, diphtheria toxin; GM-CSF, granulocyte-macrophage colony-stimulating factor; GST, glutathione S-transferase; IF, interferon; IL, interleukin; RNase, ribonuclease. known structure. We term this mode of association 3 0 domain swapping, because oligomers are formed from stable monomers by exchanging domains.A problem related to the formation of oligomeric proteins in a cell is the problem of how oligomeric proteins evolved from monomeric precursor proteins. For an oligomer to evolve, random mutations must change the surface of the monomer so that sufficient free energy is released upon oligomerization to overcome the accompanying entropy loss of immobilizing the monomers. As we discuss in this review, single amino acid replacements must be fortuitous to provide an adequate free energy of interaction. But an ...

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Three-dimensional crystal structure of recombinant murine interferon-beta.

Cited by 126 publications

References 68 publications

Threading analysis suggests that the obese gene product may be a helical cytokine

Threading analysis suggests that the obese gene product may be a helical cytokine

Homology model of human interferon‐α8 and its receptor complex

3D domain swapping: A mechanism for oligomer assembly

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