BIOC 311 Lecture Notes - Lecture 28: Hepatocyte Nuclear Factor 4, Enterohepatic Circulation, Post-Translational Modification
12 Feb 2020
School
Department
Course
Professor
Document Summary
Metabolic control has 3 parts: allosteric control, post-translational modification (usually phosphorylation, transcription of gene. Genetic evidence of the crucial role played by tfs in metabolic control. Mutation in hnf causes maturity-onset diabetes of the young (mody) We find this through studies of the receptors: get diabetes at 10 or 12 years old, hnf4 crystallography: 2 subunits, an upstream and a downstream subunit. Central zone incorporates dna-bd, lbds and the hinge region. Central zone coordinates the enzyme"s different activities. Post-translational regulation of hnf4 is important methylation of r91 in the hinge zone by prmt1 (coactivator) causes a change of conformation that increases receptor affinity for dna: activation: Phosphorylation of s78 by another signal (e. g. from glucagon, via pkc) causes a conformational change that disrupts the fold in the dbd that is required for dna binding. Mody disease: there is a mini mutation in the lbd, yes, but the leading mutation causing mody is located in the hinge region.
