Florida State University Research Foundation, Inc.

Timothy A Cross

William W Brey

Alexej I Smirnov

Eduard Y Chekmenev

David D Busath

Mukesh Sharma

Huan-Xiang Zhou

Myunggi Yi

Hao Dong

Huajun Qin

The invention relates to the atomistic functional understanding of the M2 protein from the influenza A virus. This acid-activated selective proton channel has been the subject of numerous conductance, structural, and computational studies. Previously, little was known at the atomic level about the heart of the functional mechanism of this tetrameric protein, a tetrad of HxxxW residues. The structure of the M2 conductance domain in a lipid bilayer is disclosed and displays the defining features of the native protein that have not been attainable from structures solubilized by detergents. A detailed mechanism for acid activation and proton conductance, involving a strong hydrogen bond between two adjacent histidines and specific interactions with the tryptophan gate, is provided and elucidates many observations on the M2 proton conductance.

Membrane proteins, mechanisms of action and uses thereof

Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

Solid state NMR method for screening cell membrane protein binding drug candidates

Solid-state NMR method for screening cell membrane protein binding drug candidates

Growing community of inventors

Tallahassee, FL, United States of America

Timothy A Cross