Crystal structure of the complex of human interferon-λ1 with its high affinity receptor interferon-λR1

Interferon-λ 1 (IFN-λ1, also known as IL-29) belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific hetero-dimeric receptor complexes consisting of IFN-λR1 and IL-10R2. We have determined the structure of human IFN-λ1 complexed with human IFN-λR1, a receptor unique to type III IFNs. The overall structure of IFN-λ1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-λR1 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, and loops primarily from the N-terminal domain and inter-domain hinge region of the IFN-λR1. Composition and architecture of the interface that includes only a few direct hydrogen bonds supports 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.