PDBsum entry 4wrm

Cytokine/cytokine receptor

PDB id: 4wrm

Contents

Protein chains

445 a.a.

141 a.a.

PDB id:

4wrm

Name:

Cytokine/cytokine receptor

Title:

Structure of the human csf-1:csf-1r complex

Structure:

Macrophage colony-stimulating factor 1 receptor. Chain: a. Fragment: unp residues 20-504. Synonym: csf-1 receptor,m-csf-r,proto-oncogenE C-fms. Engineered: yes. Macrophage colony-stimulating factor 1. Chain: b. Fragment: unp residues 33-181. Synonym: mcsf,lanimostim.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: csf1r, fms. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Gene: csf1. Expressed in: escherichia coli.

Resolution:

6.85Å R-factor: 0.330 R-free: 0.359

Authors:

J.Felix,S.De Munck,J.Elegheert,S.N.Savvides

Key ref:

J.Felix et al. (2015). Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1. Structure, 23, 1621-1631. PubMed id: 26235028 DOI: 10.1016/j.str.2015.06.019

Date:

24-Oct-14 Release date: 12-Aug-15

Protein chain

P07333  (CSF1R_HUMAN) -  Macrophage colony-stimulating factor 1 receptor from Homo sapiens

Seq: 972 a.a.

Struc: 445 a.a.

Protein chain

P09603  (CSF1_HUMAN) -  Macrophage colony-stimulating factor 1 from Homo sapiens

Seq: 554 a.a.

Struc: 141 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

DOI no: 10.1016/j.str.2015.06.019

Structure 23:1621-1631 (2015)

PubMed id: 26235028

Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1.

J.Felix, S.De Munck, K.Verstraete, L.Meuris, N.Callewaert, J.Elegheert, S.N.Savvides.

ABSTRACT

Human colony-stimulating factor 1 receptor (hCSF-1R) is unique among the hematopoietic receptors because it is activated by two distinct cytokines, CSF-1 and interleukin-34 (IL-34). Despite ever-growing insights into the central role of hCSF-1R signaling in innate and adaptive immunity, inflammatory diseases, and cancer, the structural basis of the functional dichotomy of hCSF-1R has remained elusive. Here, we report crystal structures of ternary complexes between hCSF-1 and hCSF-1R, including their complete extracellular assembly, and propose a mechanism for the cooperative human CSF-1:CSF-1R complex that relies on the adoption by dimeric hCSF-1 of an active conformational state and homotypic receptor interactions. Furthermore, we trace the cytokine-binding duality of hCSF-1R to a limited set of conserved interactions mediated by functionally equivalent residues on CSF-1 and IL-34 that play into the geometric requirements of hCSF-1R activation, and map the possible mechanistic consequences of somatic mutations in hCSF-1R associated with cancer.