Physics Colloquium - Fall 2007 - An Ion Channel Nanomachine
Dept of Physics & Astronomy
University of Maine, Orono, Maine
Presents
Dr. Anthony Auerbach
Professor of Physiology & Biophysics
University of Buffalo
An Ion Channel Nanomachine
Acetylcholine receptor-channels (AChRs) are large (~300 kD, five subunits) allosteric membrane proteins that switch between C(losed) and O(pen) conformations. We use F, a parameter derived from the forward (ko) and backward (kc) rate constants of a reaction, to provide temporal information about the moving parts of the AChR in C↔O ‘gating'. F is the slope of a linear fit to a plot of log ko vs log Keq (=ko/kc), for a family of mutations of a single residue. First, we develop a Markov model of the transition region (TR) and show that F reflects the relative time in the TR that the perturbed residue switches, in an all-or-none fashion, from a C-like to an O-like structure. Second, we describe the map of F-values for ~300 different AChR residues. There is, approximately, a coarse-grained and decreasing gradient in F between the allosteric (transmitter-binding) sites and the catalytic site (the ‘gate'). Third, we use this map and theory to calculate the shape of the micro-barriers of the TR, which turns out to be nearly flat. Finally, we use the ‘speed-limit' for channel-opening to estimate the rates of the microscopic transitions between the intermediates states that link stable C with stable O. AChR gating is, approximately, a brownian conformational ‘wave' in which nm-sized chunks of protein move back-and-forth (on ~50 ns timescales) to connect the stable ground states of the reaction.
Friday, October 5, 2007
3:10 pm
140 Bennett Hall
Refreshments will follow in Rm. 114, Bennett Hall
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