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Publication Abstract from PubMed

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.

Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.,Huang CS, Oberbeck N, Hsiao YC, Liu P, Johnson AR, Dixit VM, Hymowitz SG Structure. 2018 May 1;26(5):767-777.e5. doi: 10.1016/j.str.2018.04.002. Epub 2018, Apr 26. PMID:29706531^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.