title: Structural and mechanistic principles of intramembrane proteolysis--lessons from rhomboids.
abstract: Intramembrane proteases cleave membrane proteins in their transmembrane helices to regulate a wide range of biological processes. They catalyse hydrolytic reactions within the hydrophobic environment of lipid membranes where water is normally excluded. How? Do the different classes of intramembrane proteases share any mechanistic principles? In this review these questions will be discussed in view of the crystal structures of prokaryotic members of the three known catalytic types of intramembrane proteases published over the past 7 years. Rhomboids, the intramembrane serine proteases that are the best understood family, will be the initial area of focus, and the principles that have arisen from a number of structural and biochemical studies will be considered. The site-2 metalloprotease and GXGD-type aspartyl protease structures will then be discussed, with parallels drawn and differences highlighted between these enzymes and the rhomboids. Despite the significant advances achieved so far, to obtain a detailed understanding of the mechanism of any intramembrane protease, high-resolution structural information on the substrate-enzyme complex is required. This remains a major challenge for the field.
authors: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic. kvido.strisovsky@uochb.cas.cz
authors: Kvido
authors: K
authors: Strisovsky
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D057055:Aspartic Acid Proteases / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D004268:DNA-Binding Proteins / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D053763:Presenilins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D059748:Proteolysis; D057057:Serine Proteases / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D029968:Escherichia coli Proteins; C102898:GlpG protein, E coli; D008565:Membrane Proteins; D053763:Presenilins; C081481:Rho protein, Drosophila; D057055:Aspartic Acid Proteases; D010450:Endopeptidases; D057057:Serine Proteases; C432693:preflagellin peptidase; D008666:Metalloendopeptidases; C525075:S2P metalloprotease, Methanocaldococcus jannaschii