Publication Date:
2012-11-10
Description:
N-type inactivation of potassium channels is controlled by cytosolic loops that are intrinsically disordered. Recent experiments have shown that the mechanism of N-type inactivation through disordered regions can be stereospecific and vary depending on the channel type. Variations in mechanism occur despite shared coarse grain features such as the length and amino acid compositions of the cytosolic disordered regions. We have adapted a phenomenological model designed to explain how specificity in molecular recognition is achieved through disordered regions. We propose that the channel-specific observations for N-type inactivation represent distinct mechanistic choices for achieving function through conformational selection versus induced fit. It follows that the dominant mechanism for binding and specificity can be modulated through subtle changes in the amino acid sequences of disordered regions, which is interesting given that specificity in function is realized in the absence of autonomous folding. N-terminal disordered regions control inactivation of potassium channels. The mechanism of inactivation is different for BK channel versus Shaker channels. The former populates an O* state that shows intermediate activity. Adaptation of existing phenomenological models for coupled folding and binding explains channel-specific differences in N-type inactivation through disordered regions.
Print ISSN:
0265-9247
Electronic ISSN:
1521-1878
Topics:
Biology
,
Medicine
