Autoinhibitory domains of various Ca2+ transporters cross-react.
Synthetic peptides having the sequence of the calmodulin-binding autoinhibitory domain of the Na+/Ca2+ exchanger (XIP) and of the plasma membrane Ca2+ pump (C28R2) inhibited the sarcoplasmic reticulum (SERCA) and plasma membrane (PMCA) Ca2+ pumps. XIP was nearly as effective in inhibiting both systems as C28R2, which had previously been considered to be the most powerful peptide inhibitor of PMCA. In contrast, calmodulin-binding peptides from non-Ca2+ transport proteins (calmodulin-dependent protein kinase II and myosin light chain kinase) showed only weak inhibition. The relative specificity and effectiveness of the peptides from the Ca2+ transport proteins, as well as the characteristics of their actions were similar in both SERCA and PMCA, suggesting a high degree of functional relatedness between these autoinhibitory regions. Secondary structure predictions show that the calmodulin-binding autoinhibitory domains of the Na+/Ca2+ exchanger and PMCA are predicted to form a beta structure which might be necessary for the observed cross-inhibition. The results also indicate that other domains of the Ca2+ transporters have common structural elements which interact with the autoinhibitory domains.
Department of Cell Metabolism, National Institutes of Haematology and Blood Transfusion, Budapest, Hungary.
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Enyedi
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JT
Penniston
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D010446:Peptide Fragments; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium