Related Experiment Video
Updated: Aug 14, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
The role of a conserved inter-transmembrane domain interface in regulating alpha(2a)-adrenergic receptor
M H Wilson1, H A Highfield, L E Limbird
1Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract:
Functional and structural data from G protein-coupled receptors (GPCR) predict that transmembrane-domain (TM)2 is adjacent to TM7 within the GPCR structure, and that within this interface a conserved aspartate in TM2 and a conserved asparagine in TM7 exist in close proximity. Mutation at this D79(TM2)-N422(TM7) interface in the alpha(2A)-adrenergic receptor (alpha(2A)AR) affects not only receptor activation but also cell-surface residence time and conformational stability. Mutation at TM2(D79N) reduces allosteric modulation by Na(+) and receptor activation more dramatically than affecting cell-surface receptor turnover and conformational stability, whereas mutation at TM7(N422D) creates profound conformational instability and more rapid degradation of receptor from the surface of cells despite receptor activation and allosteric modulation properties that mirror a wild-type receptor. Double mutation of TM2 and 7(D79N/N422D) reveals phenotypes for receptor activation and conformational stability intermediate between the wild-type and singly mutated alpha(2A)AR. Additionally, the structural placement of a negative charge at this TM2/TM7 interface is necessary but not sufficient for receptor structural stability, because mislocalization of the negative charge in either the D79E alpha(2A)AR (which extends the charge out one methylene group) or the D79N/N422D alpha(2A)AR (placing the charge in TM7 instead of TM2) results in conformational lability in detergent solution and more rapid cell-surface receptor clearance. These studies suggest that this interface is important in regulating receptor cell-surface residence time and conformational stability in addition to its previously recognized role in receptor activation.
Related Concept Videos
Multi-pass Transmembrane Proteins and β-barrels
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Intracellular Signaling Affects Focal Adhesions
Some...
Cell Adhesion Molecules - Types and Functions
CAM Families
The Integrin family of proteins is primarily involved in a...
Tension Response at Adherens Junctions
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...

