Membrane topology of the C. elegans SEL-12 presenilin.
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.
Li
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Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Greenwald
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D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D003600:Cytosol / Q000737:chemistry; D005260:Female; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D053764:Presenilin-1; D053766:Presenilin-2; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2; C095907:SEL-12 protein, C elegans