Related Experiment Video
Updated: Jul 16, 2026

Methodology for Studying Interactions of Vitamin A Membrane Receptors and Opsin Protein with their Ligands in Generating the Retinylidene Protein
Published on: October 4, 2024
New insights into Vitamin D sterol-VDR proteolysis, allostery, structure-function from the perspective of a
Mathew T Mizwicki1, Craig M Bula, June E Bishop
1Department of Biochemistry, University of California-Riverside, Riverside, CA 92521, USA.
Abstract:
Recently, we have developed a Vitamin D sterol (VDS)-VDR conformational ensemble model. This model can be broken down into three individual, yet interlinked parts: (a) the conformationally flexible VDS, (b) the apo/holo-VDR helix-12 (H12) conformational ensemble, and (c) the presence of two VDR ligand binding pockets (LBPs); one thermodynamically favored (the genomic pocket, G-pocket) and the other kinetically favored by VDSs (the alternative pocket, A-pocket). One focus of this study is to use directed VDR mutagenesis to (1) demonstrate H12 is stabilized in the transcriptionally active closed conformation (hVDR-c1) by three salt-bridges that span the length of H12 (cationic residues R154, K264 and R402), (2) to elucidate the VDR trypsin sites [R173 (hVDR-c1), K413 (hVDR-c2) and R402 (hVDR-c3)] and (3) demonstrate the apo-VDR H12 equilibrium can be shifted. The other focus of this study is to apply the model to generate a mechanistic understanding to discrepancies observed in structure-function data obtained with a variety of 1alpha,25(OH)(2)-Vitamin D(3) (1,25D) A-ring and side-chain analogs, and side-chain metabolites. We will demonstrate that these structure-function conundrums can be rationalized, for the most part by focusing on alterations in the VDS conformational flexibility and the elementary interaction between the VDS and the VDR A- and G-pockets, relative to the control, 1,25D.
Related Concept Videos
Role of Skin in Vitamin D Synthesis
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin D3(cholecalciferol).
Protein Organization
The primary structure of a protein is its amino acid sequence.
Protein Organization
Protein Organization
Protein Organization
The primary structure of a protein is its amino acid sequence.
Structural Protein Function
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
