4EXN

Crystal structure of mouse Interleukin-34

Summary for 4EXN

• Entry DOI: 10.2210/pdb4exn/pdb
• Related: 4EXP
• Descriptor: Interleukin-34, beta-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: extended 4-helix bundle, c-fms, csf-1r, cytokine
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 4
• Total formula weight: 87612.57

Authors

Liu, H.,Leo, C.,Chen, X.,Wong, B.R.,Williams, L.T.,Lin, H.,He, X. (deposition date: 2012-04-30, release date: 2012-05-30, Last modification date: 2024-11-20)

Primary citation

Liu, H.,Leo, C.,Chen, X.,Wong, B.R.,Williams, L.T.,Lin, H.,He, X.
The mechanism of shared but distinct CSF-1R signaling by the non-homologous cytokines IL-34 and CSF-1.
Biochim.Biophys.Acta, 1824:938-945, 2012

PubMed Abstract: Interleukin-34 (IL-34) and colony stimulating factor-1 (CSF-1) both signal through the CSF-1R receptor tyrosine kinase, but they have no sequence homology, and their functions and signaling activities are not identical. We report the crystal structures of mouse IL-34 alone and in complex with the N-terminal three immunoglobulin-like domains (D1-D3) of mouse CSF-1R. IL-34 is structurally related to other helical hematopoietic cytokines, but contains two additional helices integrally associated with the four shared helices. The non-covalently linked IL-34 homodimer recruits two copies of CSF-1R on the sides of the helical bundles, with an overall shape similar to the CSF-1:CSF-1R complex, but the flexible linker between CSF-1R D2 and D3 allows these domains to clamp IL-34 and CSF-1 at different angles. Functional dissection of the IL-34:CSF-1R interface indicates that the hydrophobic interactions, rather than the salt bridge network, dominate the biological activity of IL-34. To degenerately recognize two ligands with completely different surfaces, CSF-1R apparently takes advantage of different subsets of a chemically inert surface that can be tuned to fit different ligand shapes. Differentiated signaling between IL-34 and CSF-1 is likely achieved by the relative thermodynamic independence of IL-34 vs. negative cooperativity of CSF-1 at the receptor-recognition sites, in combination with the difference in hydrophobicity which dictates a more stable IL-34:CSF-1R complex compared to the CSF-1:CSF-1R complex.

PubMed: 22579672
DOI: 10.1016/j.bbapap.2012.04.012

Experimental method

X-RAY DIFFRACTION (2.7 Å)