title: Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor.
abstract: Recent work on WW domain-containing oxidoreductase (WWOX) tumor suppressor is beginning to shed new light on both the molecular mechanism of action of its WW domains as well as the contiguous catalytic domain. Herein, the structural basis underlying the ability of WW1 domain to bind to various physiological ligands and how the orphan WW2 tandem partner synergizes its ligand binding in the context of WW1-WW2 tandem module of WWOX is discussed. Notably, the WW domains within the WW1-WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. In this manner, the association of WW2 domain with WW1 hinders ligand binding to the latter. Consequently, ligand binding to WW1 domain not only results in the displacement of WW2 lid but also disrupts the fixed orientation of WW domains in the liganded conformation. Equally importantly, structure-guided functional approach suggests that the catalytic domain of WWOX likely serves as a retinal oxidoreductase that catalyzes the reversible oxidation and reduction of all-trans-retinal. Collectively, this review provides structural insights into the functional versatility of a key signaling protein with important implications on its biology.
authors: Department of Biochemistry & Molecular Biology, Leonard Miller School of Medicine, University of Miami, Miami, FL 33136, USA amjad@farooqlab.net.
authors: Amjad
authors: A
authors: Farooq
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry* / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D012160:Retina / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology; D020080:Tandem Repeat Sequences / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000502:physiology*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: WW–ligand interactions; allosteric communication; retinal oxidoreductase; retinoid metabolism