Pinto L H, Dieckmann G R, Gandhi C S, Papworth C G, Braman J, Shaughnessy M A, Lear J D, Lamb R A, DeGrado W F
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208-3500, USA.
Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11301-6. doi: 10.1073/pnas.94.21.11301.
The M2 protein from influenza A virus forms proton-selective channels that are essential to viral function and are the target of the drug amantadine. Cys scanning was used to generate a series of mutants with successive substitutions in the transmembrane segment of the protein, and the mutants were expressed in Xenopus laevis oocytes. The effect of the mutations on reversal potential, ion currents, and amantadine resistance were measured. Fourier analysis revealed a periodicity consistent with a four-stranded coiled coil or helical bundle. A three-dimensional model of this structure suggests a possible mechanism for the proton selectivity of the M2 channel of influenza virus.
甲型流感病毒的M2蛋白形成质子选择性通道,这些通道对病毒功能至关重要,并且是药物金刚烷胺的作用靶点。利用半胱氨酸扫描在该蛋白的跨膜区段产生一系列连续替换的突变体,并将这些突变体在非洲爪蟾卵母细胞中表达。测定了这些突变对反转电位、离子电流和金刚烷胺抗性的影响。傅里叶分析揭示了与四链卷曲螺旋或螺旋束一致的周期性。该结构的三维模型提示了流感病毒M2通道质子选择性的一种可能机制。