Intramembrane protease

Intramembrane proteases (IMPs), also known as intramembrane-cleaving proteases (I-CLiPs), are enzymes that have the property of cleaving transmembrane domains of integral membrane proteins.[1][2][3] All known intramembrane proteases are themselves integral membrane proteins with multiple transmembrane domains, and they have their active sites buried within the lipid bilayer of cellular membranes.[4]

Intramembrane proteases are not evolutionarily related to classical soluble proteases, having evolved their catalytic sites by convergent evolution.[5][6]

Although only recently discovered, intramembrane proteases are the focus of intense interest because of their major biological functions and their implication in many human diseases.

Classification

Four major classes of intramembrane proteases have been discovered:[7]

Site-2 protease (S2P) and S2P-like proteases, which are metalloproteases[8]
Presenilin, the active subunit of gamma secretase, which is an aspartyl protease[9][10]
Signal peptide peptidases (SPPs) and SPP-like proteases, which are aspartyl proteases and are distantly related to presenilin but have opposite membrane orientation[11][12]
Rhomboid proteases, which are serine proteases[13]

References

Brown, MS; Ye, J; Rawson, RB; Goldstein, JL (18 February 2000). "Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans". Cell. 100 (4): 391–8. doi:10.1016/S0092-8674(00)80675-3. PMID 10693756.
Urban, S; Freeman, M (October 2002). "Intramembrane proteolysis controls diverse signalling pathways throughout evolution". Current Opinion in Genetics & Development. 12 (5): 512–8. doi:10.1016/s0959-437x(02)00334-9. PMID 12200155.
Wolfe, MS; Kopan, R (20 August 2004). "Intramembrane proteolysis: theme and variations". Science. 305 (5687): 1119–23. doi:10.1126/science.1096187. PMID 15326347.
Erez, E; Fass, D; Bibi, E (21 May 2009). "How intramembrane proteases bury hydrolytic reactions in the membrane". Nature. 459 (7245): 371–8. doi:10.1038/nature08146. PMID 19458713.
Koonin, EV; Makarova, KS; Rogozin, IB; Davidovic, L; Letellier, MC; Pellegrini, L (2003). "The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers". Genome Biology. 4 (3): R19. doi:10.1186/gb-2003-4-3-r19. PMC 153459. PMID 12620104.
Lemberg, M. K.; Freeman, M. (1 November 2007). "Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases". Genome Research. 17 (11): 1634–1646. doi:10.1101/gr.6425307. PMC 2045146. PMID 17938163.
Wolfe, M. S. (3 February 2009). "Intramembrane-cleaving Proteases". Journal of Biological Chemistry. 284 (21): 13969–13973. doi:10.1074/jbc.R800039200. PMC 2682844. PMID 19189971.
Rawson, RB; Zelenski, NG; Nijhawan, D; Ye, J; Sakai, J; Hasan, MT; Chang, TY; Brown, MS; Goldstein, JL (December 1997). "Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs". Molecular Cell. 1 (1): 47–57. doi:10.1016/s1097-2765(00)80006-4. PMID 9659902.
Wolfe, MS; Xia, W; Ostaszewski, BL; Diehl, TS; Kimberly, WT; Selkoe, DJ (8 April 1999). "Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity". Nature. 398 (6727): 513–7. doi:10.1038/19077. PMID 10206644.
De Strooper, B; Annaert, W; Cupers, P; Saftig, P; Craessaerts, K; Mumm, JS; Schroeter, EH; Schrijvers, V; Wolfe, MS; Ray, WJ; Goate, A; Kopan, R (8 April 1999). "A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain". Nature. 398 (6727): 518–22. doi:10.1038/19083. PMID 10206645.
Weihofen, A; Binns, K; Lemberg, MK; Ashman, K; Martoglio, B (21 June 2002). "Identification of signal peptide peptidase, a presenilin-type aspartic protease". Science. 296 (5576): 2215–8. doi:10.1126/science.1070925. PMID 12077416.
Friedmann, E; Hauben, E; Maylandt, K; Schleeger, S; Vreugde, S; Lichtenthaler, SF; Kuhn, PH; Stauffer, D; Rovelli, G; Martoglio, B (August 2006). "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production". Nature Cell Biology. 8 (8): 843–8. doi:10.1038/ncb1440. PMID 16829952.
Urban, S; Lee, JR; Freeman, M (19 October 2001). "Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases". Cell. 107 (2): 173–82. doi:10.1016/s0092-8674(01)00525-6. PMID 11672525.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] Brown, MS; Ye, J; Rawson, RB; Goldstein, JL (18 February 2000). "Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans". Cell. 100 (4): 391–8. doi:10.1016/S0092-8674(00)80675-3. PMID 10693756.

[2] Urban, S; Freeman, M (October 2002). "Intramembrane proteolysis controls diverse signalling pathways throughout evolution". Current Opinion in Genetics & Development. 12 (5): 512–8. doi:10.1016/s0959-437x(02)00334-9. PMID 12200155.

[3] Wolfe, MS; Kopan, R (20 August 2004). "Intramembrane proteolysis: theme and variations". Science. 305 (5687): 1119–23. doi:10.1126/science.1096187. PMID 15326347.

[4] Erez, E; Fass, D; Bibi, E (21 May 2009). "How intramembrane proteases bury hydrolytic reactions in the membrane". Nature. 459 (7245): 371–8. doi:10.1038/nature08146. PMID 19458713.

[5] Koonin, EV; Makarova, KS; Rogozin, IB; Davidovic, L; Letellier, MC; Pellegrini, L (2003). "The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers". Genome Biology. 4 (3): R19. doi:10.1186/gb-2003-4-3-r19. PMC 153459. PMID 12620104.

[6] Lemberg, M. K.; Freeman, M. (1 November 2007). "Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases". Genome Research. 17 (11): 1634–1646. doi:10.1101/gr.6425307. PMC 2045146. PMID 17938163.

[7] Wolfe, M. S. (3 February 2009). "Intramembrane-cleaving Proteases". Journal of Biological Chemistry. 284 (21): 13969–13973. doi:10.1074/jbc.R800039200. PMC 2682844. PMID 19189971.

[8] Rawson, RB; Zelenski, NG; Nijhawan, D; Ye, J; Sakai, J; Hasan, MT; Chang, TY; Brown, MS; Goldstein, JL (December 1997). "Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs". Molecular Cell. 1 (1): 47–57. doi:10.1016/s1097-2765(00)80006-4. PMID 9659902.

[9] Wolfe, MS; Xia, W; Ostaszewski, BL; Diehl, TS; Kimberly, WT; Selkoe, DJ (8 April 1999). "Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity". Nature. 398 (6727): 513–7. doi:10.1038/19077. PMID 10206644.

[10] De Strooper, B; Annaert, W; Cupers, P; Saftig, P; Craessaerts, K; Mumm, JS; Schroeter, EH; Schrijvers, V; Wolfe, MS; Ray, WJ; Goate, A; Kopan, R (8 April 1999). "A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain". Nature. 398 (6727): 518–22. doi:10.1038/19083. PMID 10206645.

[11] Weihofen, A; Binns, K; Lemberg, MK; Ashman, K; Martoglio, B (21 June 2002). "Identification of signal peptide peptidase, a presenilin-type aspartic protease". Science. 296 (5576): 2215–8. doi:10.1126/science.1070925. PMID 12077416.

[12] Friedmann, E; Hauben, E; Maylandt, K; Schleeger, S; Vreugde, S; Lichtenthaler, SF; Kuhn, PH; Stauffer, D; Rovelli, G; Martoglio, B (August 2006). "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production". Nature Cell Biology. 8 (8): 843–8. doi:10.1038/ncb1440. PMID 16829952.

[13] Urban, S; Lee, JR; Freeman, M (19 October 2001). "Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases". Cell. 107 (2): 173–82. doi:10.1016/s0092-8674(01)00525-6. PMID 11672525.

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)