PDBsum entry 4kc3

Immune system

PDB id: 4kc3

Contents

Protein chains

137 a.a.

278 a.a.

Ligands

NAG ×3

PDB id:

4kc3

Name:

Immune system

Title:

Cytokine/receptor binary complex

Structure:

Interleukin-33. Chain: a. Fragment: unp residues 112-270. Synonym: il-33, interleukin-1 family member 11, il-1f11, nuclear factor from high endothelial venules, nf-hev. Engineered: yes. Interleukin-1 receptor-like 1. Chain: b. Fragment: unp residues 19-321.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: il33, c9orf26, il1f11, nfhev. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: il1rl1, der4, st2, t1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

3.27Å R-factor: 0.241 R-free: 0.283

Authors:

X.Liu,X.Q.Wang

Key ref:

X.Liu et al. (2013). Structural insights into the interaction of IL-33 with its receptors. Proc Natl Acad Sci U S A, 110, 14918-14923. PubMed id: 23980170 DOI: 10.1073/pnas.1308651110

Date:

24-Apr-13 Release date: 28-Aug-13

Protein chain

O95760  (IL33_HUMAN) -  Interleukin-33 from Homo sapiens

Seq: 270 a.a.

Struc: 137 a.a.

Protein chain

Q01638  (ILRL1_HUMAN) -  Interleukin-1 receptor-like 1 from Homo sapiens

Seq: 556 a.a.

Struc: 278 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.3.2.2.6 - ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
• Reaction: NAD⁺ + H2O = ADP-D-ribose + nicotinamide + H⁺

NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+) (Bound ligand (Het Group name = NAG) matches with 43.75% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1073/pnas.1308651110

Proc Natl Acad Sci U S A 110:14918-14923 (2013)

PubMed id: 23980170

Structural insights into the interaction of IL-33 with its receptors.

X.Liu, M.Hammel, Y.He, J.A.Tainer, U.S.Jeng, L.Zhang, S.Wang, X.Wang.

ABSTRACT

Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.