PDBsum entry 6hgo

Immune system

PDB id: 6hgo

Contents

Protein chains

126 a.a.

Ligands

NAG-NAG

NAG ×3

SO4

Waters ×224

PDB id:

6hgo

Name:

Immune system

Title:

Crystal structure of human il-17f

Structure:

Interleukin-17f. Chain: a, b, c, d. Fragment: il-17f. Synonym: il-17f,cytokine ml-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: il17f. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s.

Resolution:

2.10Å R-factor: 0.200 R-free: 0.220

Authors:

J.M.Rondeau,A.Goepfert

Key ref:

A.Goepfert et al. (2020). Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling. Immunity, 52, 499. PubMed id: 32187518 DOI: 10.1016/j.immuni.2020.02.004

Date:

23-Aug-18 Release date: 20-Nov-19

Protein chains

Q96PD4  (IL17F_HUMAN) -  Interleukin-17F from Homo sapiens

Seq: 163 a.a.

Struc: 126 a.a.

DOI no: 10.1016/j.immuni.2020.02.004

Immunity 52:499 (2020)

PubMed id: 32187518

Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.

A.Goepfert, S.Lehmann, J.Blank, F.Kolbinger, J.M.Rondeau.

ABSTRACT

Interleukin-17A (IL-17A), IL-17F, and IL-17A/F heterodimers are key cytokines of the innate and adaptive immune response. Dysregulation of the IL-17 pathway contributes to immune pathology, and it is therefore important to elucidate the molecular mechanisms that govern IL-17 recognition and signaling. The receptor IL-17RC is thought to act in concert with IL-17RA to transduce IL-17A-, IL-17F-, and IL-17A/F-mediated signals. We report the crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F. In contrast to the expected model, we found that IL-17RC formed a symmetrical 2:1 complex with IL-17F, thus competing with IL-17RA for cytokine binding. Using biophysical techniques, we showed that IL-17A and IL-17A/F also form 2:1 complexes with IL-17RC, suggesting the possibility of IL-17RA-independent IL-17 signaling pathways. The crystal structure of the IL-17RC:IL-17F complex provides a structural basis for IL-17F signaling through IL-17RC, with potential therapeutic applications for respiratory allergy and inflammatory bowel diseases.