title: Structural principles of intramembrane proteases.
abstract: Intramembrane proteases are present in most organisms, and are used by cells to send signal across membranes, to activate growth factors, and to accomplish many other tasks that are beyond the capability of their soluble cousins. These enzymes specialize in cleaving peptide bonds that are normally embedded in cell membranes. They contain multiple membrane-spanning segments, and their catalytic residues are often found within these hydrophobic domains. In the past year, a number of important papers have been published that began to address the structural features of these membrane proteins by X-ray crystallography, electron microscopy, and biochemical methods, including the first report of an intramembrane protease crystal structure, that of Escherichia coli GlpG. Taken together, these studies started to reveal patterns of how intramembrane proteases are constructed, how waters are supplied to the membrane-embedded active site, and how membrane protein substrates interact with them.
authors: Department of Pharmacology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. ya.ha@yale.edu
authors: Ya
authors: Y
authors: Ha
mesh_terms: D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C102898:GlpG protein, E coli; D008565:Membrane Proteins; D014867:Water; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D010447:Peptide Hydrolases
references: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14765-70
references: 10611287
references: Nat Struct Mol Biol. 2006 Dec;13(12):1084-91
references: 17099694
references: Nature. 2000 Sep 7;407(6800):48-54
references: 10993067
references: Physiol Rev. 2001 Apr;81(2):741-66
references: 11274343
references: Cell. 2001 Oct 19;107(2):173-82
references: 11672525
references: Science. 2002 Jun 21;296(5576):2215-8
references: 12077416
references: Nature. 2003 Mar 27;422(6930):438-41
references: 12660785
references: EMBO J. 2004 Feb 11;23(3):483-8
references: 14749724
references: J Cell Biol. 2004 Apr 26;165(2):167-73
references: 15096522
references: Science. 2004 Aug 20;305(5687):1119-23
references: 15326347
references: Nature. 1995 Sep 28;377(6547):351-4
references: 7566091
references: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2095-7
references: 9122152
references: Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7109-14
references: 9618547
references: Mol Cell. 1997 Dec;1(1):47-57
references: 9659902
references: Nature. 1999 Apr 8;398(6727):513-7
references: 10206644
references: Nature. 1999 Apr 8;398(6727):518-22
references: 10206645
references: J Biol Chem. 1999 Jul 30;274(31):21973-80
references: 10419520
references: Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1883-8
references: 15684070
references: EMBO J. 2005 Feb 9;24(3):464-72
references: 15616571
references: Biochem Biophys Res Commun. 2006 May 5;343(2):525-34
references: 16546128
references: Proc Natl Acad Sci U S A. 2006 May 2;103(18):6889-94
references: 16636269
references: J Biol Chem. 2006 Sep 15;281(37):27633-42
references: 16844686
references: Nature. 2006 Nov 9;444(7116):179-80
references: 17051161
references: J Neurosci. 2006 Nov 15;26(46):12081-8
references: 17108181
references: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):462-6
references: 17190827
references: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):750-4
references: 17210913
references: J Biol Chem. 2007 Feb 16;282(7):4553-60
references: 17179147
references: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2098-102
references: 17277078
references: Mol Microbiol. 2007 Apr;64(2):435-47
references: 17493126
references: Cell. 2000 Feb 18;100(4):391-8
references: 10693756