Positive charge modifications alter the ability of xip to inhibit
the plasma membrane calcium pump.
Wanyan, Xu, Craig Gatto and Mark A. Milanick.
Department of Physiology, School of Medicine, and Dalton
Cardiovascular Research Center, University of Missouri-Columbia,
Columbia, Missouri 65212
APStracts 3:0093C, 1996.
XIP (RRLLFYKYVYKRYRAGKQRG) is the shortest peptide that inhibits the
PMCA (plasma membrane Ca pump) at high Ca (J.Biol.Chem. 264,:12313
-12321). Sulfosuccinimidyl acetate (SNA) modified XIP does not inhibit
the Ca pump; SNA neutralizes the positive charge on Lys at positions
7, 11 and 17. Peptide 2CKXIP (RRLLFYRYVYRCYCAGRQKG) inhibits the
pump, but the iodoacetamido modified peptide does not inhibit. Three
peptide analogs, in which 7, 11 and 17 were Ala, Cys, or Lys,
inhibited about as well as XIP. SNA modification of these analogs
(each with 1 Lys) did not inhibit. SNA modification of 2CK-XIP
results in a peptide that does not inhibit, thus position 19 is
important. Our results suggest that it is critical that position 19
be positively charged, that positions 7, 11, and 17 are important
contact points between XIP and the Ca pump (and at least one needs to
be positively charged) and that, while it is not essential that
residues 12 and 14 be positive, they cannot be negative.
Received 18 January 1996; accepted in final form 13 March 1996.
APS Manuscript Number C27-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96