8CR8

human Interleukin-23

Summary for 8CR8

• Entry DOI: 10.2210/pdb8cr8/pdb
• Related: 8C7M 8CR5 8CR6
• Descriptor: Interleukin-12 subunit beta, Interleukin-23 subunit alpha, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: heterodimer, cytokine, extracellular, inflammation, fibronectin type iii
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 59590.77

Authors

Bloch, Y.,Savvides, S.N. (deposition date: 2023-03-08, release date: 2024-02-07, Last modification date: 2024-11-06)

Primary citation

Bloch, Y.,Felix, J.,Merceron, R.,Provost, M.,Symakani, R.A.,De Backer, R.,Lambert, E.,Mehdipour, A.R.,Savvides, S.N.
Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23.
Nat.Struct.Mol.Biol., 31:591-597, 2024

PubMed Abstract: Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12-receptor interaction interfaces, in contrast to IL-23-receptor complexes. Here we report structures of fully assembled mouse IL-12/human IL-23-receptor complexes comprising the complete extracellular segments of the cognate receptors determined by electron cryo-microscopy. The structures reveal key commonalities but also surprisingly diverse features. Most notably, whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig domain of their high-affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell membrane. Collectively, our findings will help to complete our understanding of cytokine-mediated assemblies of tall cytokine receptors and will enable a cytokine-specific interrogation of IL-12/IL-23 signaling in physiology and disease.

PubMed: 38287195
DOI: 10.1038/s41594-023-01190-6

Experimental method

X-RAY DIFFRACTION (2 Å)