Structural principles of intramembrane proteases.
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.
Ha
Ya
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Department of Pharmacology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. ya.ha@yale.edu
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
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
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