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You are here: Home Administration Chemistry & Biochemistry Department Events October 2017 Biochemistry Seminar: Mei Hong, "Structure and assembly of membrane proteins and amyloid fibrils from solid-state NMR"

Biochemistry Seminar: Mei Hong, "Structure and assembly of membrane proteins and amyloid fibrils from solid-state NMR"

Mei Hong, Professor, Dept of Chemistry, MIT, Cambridge, MA, "Structure and assembly of membrane proteins and amyloid fibrils from solid-state NMR"
When Oct 18, 2017
from 12:00 PM to 01:00 PM
Where CUNY ASRC Main Auditorium
Contact Name
Contact Phone 212-650-8803
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ABSTRACT

The influenza M2 protein forms an acid-activated tetrameric proton channel that acidifies the virion to initiate virus uncoating. Using solid-state NMR, we have measured 15N and 13C chemical shifts of the proton-selective histidine residue in M2 to determine the protonation equilibria and proton exchange kinetics of the channel in near-native virus-mimetic lipid membrane. Influenza A and B viruses’ M2 proteins share little sequence homology except for a conserved HxxxW motif. Comparison of the histidine structure and dynamics in the two proteins show significant differences in the protonation equilibria, revealing interesting differences in the pH activation of the two channels. The conserved tryptophan in the transmembrane domain is the gating residue that ensures asymmetric conductance of the protons from the N-terminus to the C-terminus. Using a tryptophan-to-phenylalanine mutation, we have now obtained atomic evidence of C-terminal acid activation of the histidine. This reverse protonation is further evidenced by persistence of histidine protonation even when the N-terminal half of the channel is blocked by an antiviral drug. In addition to its proton channel function, M2 mediates membrane scission during virus budding, and this function occurs in a cholesterol-dependent fashion. We have now determined the structure of the cholesterol-binding site of M2 by simultaneous distance and orientational measurements. The result not only reveals how cholesterol is complexed to M2, but also shows unexpected binding stoichiometry, which gives novel insight into how M2 may mediate membrane scission. Solid-state NMR not only can provide atomic-resolution structural information about membrane proteins and their complexes with ligands, but can also elucidate amyloid fibril structures. I will describe the first structure determination of a metal-bound amyloid fibril, where the zinc-binding geometry leads to an unprecedented metal-peptide framework that explains the catalytic function of the protein as well as the stability of this functional amyloid.

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