Membrane topology of the C. elegans SEL-12 presenilin
1Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Abstract:
Mutant presenilins cause Alzheimer's disease. Presenilins have multiple hydrophobic regions that could theoretically span a membrane, and a knowledge of the membrane topology is crucial for deducing the mechanism of presenilin function. By analyzing the activity of beta-galactosidase hybrid proteins expressed in C. elegans, we show that the C. elegans SEL-12 presenilin has eight transmembrane domains and that there is a cleavage site after the sixth transmembrane domain. We examine the presenilin sequence in view of the predicted topology and discuss possible mechanisms for presenilin function.
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