Biochemistry, Biophysics, and Structural Biology Commons^™

A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity To Cholesterol, And Perturbed Interdomain Coupling, A. L. Herneisen, I. D. Sahu, R. M. Mccarrick, J. B. Feix, G. A. Lorigan, Kathleen P. Howard

Chemistry & Biochemistry Faculty Works

Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with alanine substitutions in the C-terminal amphipathic helix is deficient in viral scission. With the goal of providing atomic-level understanding of how the wild-type protein functions, we used a multipronged site-directed spin labeling electron paramagnetic resonance spectroscopy (SDSL-EPR) approach to characterize the conformational properties of the alanine mutant. We spin-labeled sites in the transmembrane (TM) domain and the C-terminal amphipathic helix (AH) of wild-type (WT) and mutant M2, and collected information on line shapes, relaxation rates, membrane …