Serial perturbation of MinK in I_Ks implies an -helical transmembrane span traversing the channel corpus

¹ Yale University
² University of Chicago

^* To whom correspondence should be addressed. E-mail: sangoldstein{at}uchicago.edu.

Submitted on March 29, 2007
Revised on April 17, 2007
Accepted on 22 May 2007

	Abstract

I_Ks channels contain 4 pore-forming KCNQ1 subunits and 2 accessory MinK subunits. MinK influences surface expression, voltage-dependence of gating, conduction, and pharmacology to yield the attributes characteristic of native channels in heart. The structure and location of the MinK transmembrane domain (TMD) remains a matter of scrutiny. As perturbation of gating analysis has correctly inferred the peripheral location and -helical nature of TMDs in pore-forming subunits, the method is applied here to human MinK. Tryptophan and Asparagine substitution at 23 consecutive sites yields perturbation with -helical periodicity (residues 44-56) followed by an alternating impact pattern (56-63). Arginine substitution across the span suggests that as few as 8 sites are occluded from aqueous solution (50-57). We favor a TMD model that is -helical with the external portion of the span at a lipid-protein boundary and the inner portion within the channel corpus in complex interactions.

Key Words: KCNE1, KCNQ1, KvLQT1, MiRP, MinK, potassium

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