Crystal Structure of Human Interferon-λ1 in Complex with Its High-Affinity Receptor Interferon-λR1

JOURNAL OF MOLECULAR BIOLOGY

卷:404

Article

Miknis, Zachary J.¹  Magracheva, Eugenia^1,2  Li, Wei³  Zdanov, Alexander¹  Kotenko, Sergei V.³  Wlodawer, Alexander¹ 

[1] NCI Frederick, Macromol Crystallog Lab, Frederick, MD 21702 USA

[2] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA

[3] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp Canc Ctr, Dept Biochem & Mol Biol, Newark, NJ 07103 USA

关键词: cytokine;    crystallography;    antiviral;    immunity;    signaling;   

DOI  :  10.1016/j.jmb.2010.09.068

来源: Elsevier

【 摘 要 】

Interferon (IFN)-lambda 1 [also known as interleukiun (IL)-29] belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific heterodimeric receptor complexes consisting of IFN-lambda R1 and IL-10R2. We have determined the structure of human IFN-lambda 1 complexed with human IFN-lambda R1, a receptor unique to type III IFNs. The overall structure of IFN-lambda 1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-lambda R1 consists of two distinct domains having fibronectin type III topology. The ligand receptor interface includes helix A, loop AB, and helix F on the IFN site, as well as loops primarily from the N-terminal domain and inter-domain hinge region of IFN-lambda R1. Composition and architecture of the interface that includes only a few direct hydrogen bonds support an idea that long-range ionic interactions between ligand and receptor govern the process of initial recognition of the molecules while hydrophobic interactions finalize it. Published by Elsevier Ltd.

【 授权许可】

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