TY - JOUR
T1 - The role of NH2-terminal positive charges in the activity of inward rectifier KATP channels
AU - Cukras, C. A.
AU - Jeliazkova, I.
AU - Nichols, C. G.
PY - 2002/9
Y1 - 2002/9
N2 - Approximately half of the NH2 terminus of inward rectifier (Kir) channels can be deleted without significant change in channel function, but activity is lost when more than ∼30 conserved residues before the first membrane spanning domain (M1) are removed. Systematic replacement of the positive charges in the NH2 terminus of Kir6.2 with alanine reveals several residues that affect channel function when neutralized. Certain mutations (R4A, R5A, R16A, R27A, R39A, K47A, R50A, R54A, K67A) change open probability, whereas an overlapping set of mutants (R16A, R27A, K39A, K47A, R50A, R54A, K67A) change ATP sensitivity. Further analysis of the latter set differentiates mutations that alter ATP sensitivity as a consequence of altered open state stability (R16A, K39A, K67A) from those that may affect ATP binding directly (K47A, R50A, R54A). The data help to define the structural determinants of Kir channel function, and suggest possible structural motifs within the NH2 terminus, as well as the relationship of the NH2 terminus with the extended cytoplasmic COOH terminus of the channel.
AB - Approximately half of the NH2 terminus of inward rectifier (Kir) channels can be deleted without significant change in channel function, but activity is lost when more than ∼30 conserved residues before the first membrane spanning domain (M1) are removed. Systematic replacement of the positive charges in the NH2 terminus of Kir6.2 with alanine reveals several residues that affect channel function when neutralized. Certain mutations (R4A, R5A, R16A, R27A, R39A, K47A, R50A, R54A, K67A) change open probability, whereas an overlapping set of mutants (R16A, R27A, K39A, K47A, R50A, R54A, K67A) change ATP sensitivity. Further analysis of the latter set differentiates mutations that alter ATP sensitivity as a consequence of altered open state stability (R16A, K39A, K67A) from those that may affect ATP binding directly (K47A, R50A, R54A). The data help to define the structural determinants of Kir channel function, and suggest possible structural motifs within the NH2 terminus, as well as the relationship of the NH2 terminus with the extended cytoplasmic COOH terminus of the channel.
KW - ATP
KW - K
KW - K current
KW - Kir6.2
KW - PIP
UR - http://www.scopus.com/inward/record.url?scp=0036707499&partnerID=8YFLogxK
U2 - 10.1085/jgp.20028621
DO - 10.1085/jgp.20028621
M3 - Article
C2 - 12198096
AN - SCOPUS:0036707499
SN - 0022-1295
VL - 120
SP - 437
EP - 446
JO - Journal of General Physiology
JF - Journal of General Physiology
IS - 3
ER -