NDLI: Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease.

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Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease.

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Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Davé, U. P. Brown, M. S. Goldstein, J. L. Ye, J. Grishin, N. V.
Description	Author Affiliation: Ye J ( Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046, USA.);
Abstract	The NH(2)-terminal domains of membrane-bound sterol regulatory element-binding proteins (SREBPs) are released into the cytosol by regulated intramembrane proteolysis, after which they enter the nucleus to activate genes encoding lipid biosynthetic enzymes. Intramembrane proteolysis is catalyzed by Site-2 protease (S2P), a hydrophobic zinc metalloprotease that cleaves SREBPs at a membrane-embedded leucine-cysteine bond. In the current study, we use domain-swapping methods to localize the residues within the SREBP-2 membrane-spanning segment that are required for cleavage by S2P. The studies reveal a requirement for an asparagine-proline sequence in the middle third of the transmembrane segment. We propose a model in which the asparagine-proline sequence serves as an NH(2)-terminal cap for a portion of the transmembrane alpha-helix of SREBP, allowing the remainder of the alpha-helix to unwind partially to expose the peptide bond for cleavage by S2P.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Chemistry Metabolism Dipeptides Endopeptidases Nuclear Proteins Transcription Factors Amino Acid Sequence Animals Binding Sites Cell Line Cell Membrane Conserved Sequence Cricetinae Helix-Loop-Helix Motifs Models, Molecular Molecular Sequence Data Protein Structure, Secondary Recombinant Fusion Proteins Sequence Alignment Sequence Homology, Amino Acid Sterol Regulatory Element Binding Protein 1 Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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