Presenilin mutations line up along transmembrane alpha-helices.
Presenilin 1 mutations are the major cause of autosomal dominant Alzheimer's disease. Here we present evidence that pathogenic mutations in putative transmembrane domains 1, 2, 3, 4 and 6 align along helical faces, thus supporting the view that these are indeed transmembrane domains, and suggesting that disruption of the alignment of these domains is responsible for the pathogenicity of the mutations.
Hardy
J
J
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. hardy@mayo.edu
Crook
R
R
D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D009154:Mutation; D053764:Presenilin-1; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1