Protein topology of presenilin 1.
Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.
Doan
A
A
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Thinakaran
G
G
Borchelt
D R
DR
Slunt
H H
HH
Ratovitsky
T
T
Podlisny
M
M
Selkoe
D J
DJ
Seeger
M
M
Gandy
S E
SE
Price
D L
DL
Sisodia
S S
SS
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics; D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000502:physiology; D019556:COS Cells / Q000737:chemistry / Q000502:physiology; D006224:Cricetinae; D003593:Cytoplasm / Q000737:chemistry; D005091:Exons / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D009154:Mutation / Q000502:physiology; D053764:Presenilin-1; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins