5WNK

Crystal structure of murine receptor-interacting protein 4 (Ripk4) D143N bound to TG100-115

Summary for 5WNK

• Entry DOI: 10.2210/pdb5wnk/pdb
• Related: 5WNI 5WNJ 5WNL 5WNM
• Descriptor: Receptor-interacting serine/threonine-protein kinase 4, CHLORIDE ION, 3,3'-(2,4-diaminopteridine-6,7-diyl)diphenol, ... (4 entities in total)
• Functional Keywords: kinase, inhibitor, complex, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm: Q9ERK0
• Total number of polymer chains: 1
• Total formula weight: 39369.83

Authors

Huang, C.S.,Hymowitz, S.G. (deposition date: 2017-08-01, release date: 2018-05-09, Last modification date: 2024-03-13)

Primary citation

Huang, C.S.,Oberbeck, N.,Hsiao, Y.C.,Liu, P.,Johnson, A.R.,Dixit, V.M.,Hymowitz, S.G.
Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.
Structure, 26:767-, 2018

PubMed Abstract: Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease.

PubMed: 29706531
DOI: 10.1016/j.str.2018.04.002

Experimental method

X-RAY DIFFRACTION (3.11 Å)