Protein Topology of Presenilin 1

نویسندگان

  • Andrew Doan
  • Gopal Thinakaran
  • David R Borchelt
  • Hilda H Slunt
  • Tamara Ratovitsky
  • Marcia Podlisny
  • Dennis J Selkoe
  • Mary Seeger
  • Samuel E Gandy
  • Donald L Price
  • Sangram S Sisodia
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A novel transmembrane topology of presenilin based on reconciling experimental and computational evidence.

The transmembrane topology of presenilins is still the subject of debate despite many experimental topology studies using antibodies or gene fusions. The results from these studies are partly contradictory and consequently several topology models have been proposed. Studies of presenilin-interacting proteins have produced further contradiction, primarily regarding the location of the C-terminus...

متن کامل

Topology Prediction of Membrane Proteins: Why, How and When?

Reliability measures for membrane protein topology prediction algorithms. Topology models for 37 Saccharomyces cerevisiae membrane proteins based on C-terminal reporter fusions and predictions. Experimentally based topology models for E. coli inner membrane proteins. A global topology map of the Saccharomyces cerevisiae membrane proteome. Experimentally constrained topology models for 51,208 ba...

متن کامل

Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins.

Presenilins have been implicated in the genesis of Alzheimer's disease and in facilitating LIN-12/Notch activity during development. All presenilins have multiple hydrophobic regions that could theoretically span a membrane, and a description of the membrane topology is a crucial step toward deducing the mechanism of presenilin function. Previously, we proposed an eight-transmembrane-domain mod...

متن کامل

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 d...

متن کامل

Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space.

The polytopic membrane protein presenilin 1 (PS1) is a component of the gamma-secretase complex that is responsible for the intramembranous cleavage of several type I transmembrane proteins, including the beta-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset familial Alzheimer's disease. PS1 contains...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Neuron

دوره 17  شماره 

صفحات  -

تاریخ انتشار 1996