Sortaza

Porodica sortaza
Sortaza C streptokoka grupe B povezana s pilusom. PDB pristup 3O0P
Identifikatori
Simbol	Sortaza

Sortaza se odnosi na skupinu prokariotskih enzima koji modificiraju površinske proteine, prepoznavanjem i cijepanjem karboksilnog terminala sortirajući signal. Za većinu supstrata enzima sortaze, signal prepoznavanja sastoji se od motiva LPXTG (Leu-Pro-bilo koji-Thr-Gly), zatim visoko hidrofobnog transmembranske sekvence, nakon čega slijedi skupina baznih ostataka kao što je argininski. Do cijepanja dolazi između Thr i Gly, s prolaznim vezanjem preko Thr ostatka na Cys ostatak aktivnog mjesta, nakon čega slijedi transpeptidacija koja kovalentno veže protein na komponente ćelijskog zida. Sortaze se javljaju u gotovo svim Gram-pozitivnim bakterijama i povremenim Gram-negativnim bakterijama (npr. Shewanella putrefaciens) ili Archaea (npr. Methanobacterium thermoautotrophicum), gdje dekoracija ćelijskog zida posredovana LPXTG-om nije prijavljena. Iako sortaza A, sortaza za "kućno održavanje", obično djeluje na mnoge proteinske mete, drugi oblici sortaze prepoznaju varijante oblika motiva cijepanja ili kataliziraju sklapanje pilina u pilusima.

Reakcija

Sortaza Staphylococcus aureus je transpeptidaza koja veže površinske proteine na ćelijski zid; cijepa se između Gly i Thr motiva LPXTG i katalizira stvaranje amidne veze između karboksilne skupine treonina i amino skupine peptidoglikana ćelijskog zida.

Biološka uloga

Proteini supstrata vezani sortazama za ćelijske zidove uključuju enzime, piline i glikoproteine velike površine koji posreduju adheziju. Ovi proteini često imaju važnu ulogu u virulenciji, infekcijama i kolonizaciji patogena.

Površinski proteini ne samo da podstiču interakciju između invazivnog patogena i životinjskih tkiva, već također pružaju genijalne strategije za bijeg bakterija od imunskog odgovora domaćina. U slučaju S. aureus, protein A, imunoglobulini se hvataju na površini mikroba i kamufliraju bakterije tokom invazije tkiva domaćina. S. aureus mutanti kojima nedostaje gen srtA ne uspijevaju se usidriti i prikazati neke površinske proteine te im je smanjena sposobnost izazivanja infekcija kod životinja. Sortaza djeluje na površinske proteine koji se iniciraju u put sekrecije (Sec) i čiji signalni peptid uklanja signalna peptidaza. S. aureus genom kodira dva skupa gena sortaze i gena za lučenje. Zamislivo je da S. aureus razvio je više od jednog puta za transport 20 površinskih proteina do ovojnice ćelijskog zida.

Treba imati na umu da su egzosortaza i arheosortaza funkcionalno analogne, iako ni na koji način nisu homologne sortazi.

Kao cilj antibiotika

Smatra se da su sortaze dobre mete za nove antibiotike budući da su važni proteini za patogene bakterije i barem jedna kompanija zabilježila je ograničeni komercijalni interes.

Struktura

Ova skupina cistein-peptidaza pripada porodici MEROPS peptidaza C60 (klan C-) i uključuje članove nekoliko potporodica sortaza.

Druga potporodica sortaza (C60B u MEROPS) sadrži proteine bakterijske sortaze B koji su dugi po oko 200 ostataka.

Upotreba u strukturnoj biologiji

Transpeptidaznu aktivnost sortaze koriste strukturni biolozi za proizvodnju fuzijskih proteina in vitro. Motiv prepoznavanja (LPXTG) dodaje se na C-kraj proteina od interesa, dok se motiv oligo-glicina dodaje na N-terminal drugog proteina koji se vezuje. Nakon dodavanja sortaze u proteinsku smjesu, dva peptida su kovalentno vezana putem nativne peptidne veze. Ovu reakciju koriste NMR spektroskopisti za proizvodnju NMR nevidljivih oznaka topljivosti and in one example by X-ray crystallographers to promote complex formation.

Također pogledajte

• Proteinska oznaka
• Bioinženjerstvo
• HaloTag
• Inteini

Dopunska literatura

• PDB 3O0P; Cozzi R, Malito E, Nuccitelli A, D'Onofrio M, Martinelli M, Ferlenghi I, Grandi G, Telford JL, Maione D, Rinaudo CD (juni 2011). "Structure analysis and site-directed mutagenesis of defined key residues and motives for pilus-related sortase C1 in group B Streptococcus". FASEB Journal. 25 (6): 1874–86. doi:10.1096/fj.10-174797. hdl:11562/349253. PMID 21357525. S2CID 28182632.
• Kang HJ, Paterson NG, Gaspar AH, Ton-That H, Baker EN (oktobar 2009). "The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 16967–71. Bibcode:2009PNAS..10616967K. doi:10.1073/pnas.0906826106. PMC 2761350. PMID 19805181.
• Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, Satokari R, Vesterlund S, Hendrickx AP, Lebeer S, De Keersmaecker SC, Vanderleyden J, Hämäläinen T, Laukkanen S, Salovuori N, Ritari J, Alatalo E, Korpela R, Mattila-Sandholm T, Lassig A, Hatakka K, Kinnunen KT, Karjalainen H, Saxelin M, Laakso K, Surakka A, Palva A, Salusjärvi T, Auvinen P, de Vos WM (oktobar 2009). "Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 17193–8. Bibcode:2009PNAS..10617193K. doi:10.1073/pnas.0908876106. PMC 2746127. PMID 19805152.
• Neiers F, Madhurantakam C, Fälker S, Manzano C, Dessen A, Normark S, Henriques-Normark B, Achour A (oktobar 2009). "Two crystal structures of pneumococcal pilus sortase C provide novel insights into catalysis and substrate specificity". Journal of Molecular Biology. 393 (3): 704–16. doi:10.1016/j.jmb.2009.08.058. PMID 19729023.
• Sillanpää J, Nallapareddy SR, Qin X, Singh KV, Muzny DM, Kovar CL, Nazareth LV, Gibbs RA, Ferraro MJ, Steckelberg JM, Weinstock GM, Murray BE (novembar 2009). "A collagen-binding adhesin, Acb, and ten other putative MSCRAMM and pilus family proteins of Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis Group, biotype I)". Journal of Bacteriology. 191 (21): 6643–53. doi:10.1128/JB.00909-09. PMC 2795296. PMID 19717590.
• Kang HJ, Paterson NG, Baker EN (august 2009). "Expression, purification, crystallization and preliminary crystallographic analysis of SpaA, a major pilin from Corynebacterium diphtheriae". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 65 (Pt 8): 802–4. doi:10.1107/S1744309109027596. PMC 2720338. PMID 19652344.
• Guttilla IK, Gaspar AH, Swierczynski A, Swaminathan A, Dwivedi P, Das A, Ton-That H (septembar 2009). "Acyl enzyme intermediates in sortase-catalyzed pilus morphogenesis in gram-positive bacteria". Journal of Bacteriology. 191 (18): 5603–12. doi:10.1128/JB.00627-09. PMC 2737948. PMID 19592583.
• Suree N, Liew CK, Villareal VA, Thieu W, Fadeev EA, Clemens JJ, Jung ME, Clubb RT (septembar 2009). "The structure of the Staphylococcus aureus sortase-substrate complex reveals how the universally conserved LPXTG sorting signal is recognized". The Journal of Biological Chemistry. 284 (36): 24465–77. doi:10.1074/jbc.M109.022624. PMC 2782039. PMID 19592495.
• Kang HJ, Baker EN (juli 2009). "Intramolecular isopeptide bonds give thermodynamic and proteolytic stability to the major pilin protein of Streptococcus pyogenes". The Journal of Biological Chemistry. 284 (31): 20729–37. doi:10.1074/jbc.M109.014514. PMC 2742838. PMID 19497855.
• Schlüter S, Franz CM, Gesellchen F, Bertinetti O, Herberg FW, Schmidt FR (august 2009). "The high biofilm-encoding Bee locus: a second pilus gene cluster in Enterococcus faecalis?". Current Microbiology. 59 (2): 206–11. doi:10.1007/s00284-009-9422-y. PMID 19459002. S2CID 26466809.
• Quigley BR, Zähner D, Hatkoff M, Thanassi DG, Scott JR (juni 2009). "Linkage of T3 and Cpa pilins in the Streptococcus pyogenes M3 pilus". Molecular Microbiology. 72 (6): 1379–94. doi:10.1111/j.1365-2958.2009.06727.x. PMID 19432798. S2CID 38103981.
• Solovyova AS, Pointon JA, Race PR, Smith WD, Kehoe MA, Banfield MJ (februar 2010). "Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes". European Biophysics Journal. 39 (3): 469–80. doi:10.1007/s00249-009-0432-2. PMID 19290517. S2CID 31626449.
• Budzik JM, Oh SY, Schneewind O (maj 2009). "Sortase D forms the covalent bond that links BcpB to the tip of Bacillus cereus pili". The Journal of Biological Chemistry. 284 (19): 12989–97. doi:10.1074/jbc.M900927200. PMC 2676031. PMID 19269972.
• Kang HJ, Middleditch M, Proft T, Baker EN (decembar 2009). "Isopeptide bonds in bacterial pili and their characterization by X-ray crystallography and mass spectrometry". Biopolymers. 91 (12): 1126–34. doi:10.1002/bip.21170. PMID 19226623. S2CID 1546055.
• Manzano C, Contreras-Martel C, El Mortaji L, Izoré T, Fenel D, Vernet T, Schoehn G, Di Guilmi AM, Dessen A (decembar 2008). "Sortase-mediated pilus fiber biogenesis in Streptococcus pneumoniae". Structure. 16 (12): 1838–48. doi:10.1016/j.str.2008.10.007. PMID 19081060.
• Proft T, Baker EN (februar 2009). "Pili in Gram-negative and Gram-positive bacteria - structure, assembly and their role in disease". Cellular and Molecular Life Sciences. 66 (4): 613–35. doi:10.1007/s00018-008-8477-4. PMID 18953686. S2CID 860681.
• Budzik JM, Oh SY, Schneewind O (decembar 2008). "Cell wall anchor structure of BcpA pili in Bacillus anthracis". The Journal of Biological Chemistry. 283 (52): 36676–86. doi:10.1074/jbc.M806796200. PMC 2605976. PMID 18940793.
• Mandlik A, Das A, Ton-That H (septembar 2008). "The molecular switch that activates the cell wall anchoring step of pilus assembly in gram-positive bacteria". Proceedings of the National Academy of Sciences of the United States of America. 105 (37): 14147–52. doi:10.1073/pnas.0806350105. PMC 2734112. PMID 18779588.
• Fälker S, Nelson AL, Morfeldt E, Jonas K, Hultenby K, Ries J, Melefors O, Normark S, Henriques-Normark B (novembar 2008). "Sortase-mediated assembly and surface topology of adhesive pneumococcal pili". Molecular Microbiology. 70 (3): 595–607. doi:10.1111/j.1365-2958.2008.06396.x. PMC 2680257. PMID 18761697.
• Budzik JM, Marraffini LA, Souda P, Whitelegge JP, Faull KF, Schneewind O (juli 2008). "Amide bonds assemble pili on the surface of bacilli". Proceedings of the National Academy of Sciences of the United States of America. 105 (29): 10215–20. Bibcode:2008PNAS..10510215B. doi:10.1073/pnas.0803565105. PMC 2481347. PMID 18621716.
• Nobbs AH, Rosini R, Rinaudo CD, Maione D, Grandi G, Telford JL (august 2008). "Sortase A utilizes an ancillary protein anchor for efficient cell wall anchoring of pili in Streptococcus agalactiae". Infection and Immunity. 76 (8): 3550–60. doi:10.1128/IAI.01613-07. PMC 2493207. PMID 18541657.
• Bagnoli F, Moschioni M, Donati C, Dimitrovska V, Ferlenghi I, Facciotti C, Muzzi A, Giusti F, Emolo C, Sinisi A, Hilleringmann M, Pansegrau W, Censini S, Rappuoli R, Covacci A, Masignani V, Barocchi MA (august 2008). "A second pilus type in Streptococcus pneumoniae is prevalent in emerging serotypes and mediates adhesion to host cells". Journal of Bacteriology. 190 (15): 5480–92. doi:10.1128/JB.00384-08. PMC 2493256. PMID 18515415.
• Zähner D, Scott JR (januar 2008). "SipA is required for pilus formation in Streptococcus pyogenes serotype M3". Journal of Bacteriology. 190 (2): 527–35. doi:10.1128/JB.01520-07. PMC 2223711. PMID 17993527.
• Swaminathan A, Mandlik A, Swierczynski A, Gaspar A, Das A, Ton-That H (novembar 2007). "Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriae". Molecular Microbiology. 66 (4): 961–74. doi:10.1111/j.1365-2958.2007.05968.x. PMC 2841690. PMID 17919283.
• Budzik JM, Marraffini LA, Schneewind O (oktobar 2007). "Assembly of pili on the surface of Bacillus cereus vegetative cells". Molecular Microbiology. 66 (2): 495–510. doi:10.1111/j.1365-2958.2007.05939.x. PMID 17897374.
• Kemp KD, Singh KV, Nallapareddy SR, Murray BE (novembar 2007). "Relative contributions of Enterococcus faecalis OG1RF sortase-encoding genes, srtA and bps (srtC), to biofilm formation and a murine model of urinary tract infection". Infection and Immunity. 75 (11): 5399–404. doi:10.1128/IAI.00663-07. PMC 2168291. PMID 17785477.
• Manetti AG, Zingaretti C, Falugi F, Capo S, Bombaci M, Bagnoli F, Gambellini G, Bensi G, Mora M, Edwards AM, Musser JM, Graviss EA, Telford JL, Grandi G, Margarit I (maj 2007). "Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation". Molecular Microbiology. 64 (4): 968–83. doi:10.1111/j.1365-2958.2007.05704.x. PMID 17501921. S2CID 28856933.
• Mandlik A, Swierczynski A, Das A, Ton-That H (april 2007). "Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells". Molecular Microbiology. 64 (1): 111–24. doi:10.1111/j.1365-2958.2007.05630.x. PMC 2844904. PMID 17376076.
• Nallapareddy SR, Singh KV, Sillanpää J, Garsin DA, Höök M, Erlandsen SL, Murray BE (oktobar 2006). "Endocarditis and biofilm-associated pili of Enterococcus faecalis". The Journal of Clinical Investigation. 116 (10): 2799–807. doi:10.1172/JCI29021. PMC 1578622. PMID 17016560.
• Scott JR, Zähner D (oktobar 2006). "Pili with strong attachments: Gram-positive bacteria do it differently". Molecular Microbiology. 62 (2): 320–30. doi:10.1111/j.1365-2958.2006.05279.x. PMID 16978260. S2CID 25384605.
• Swierczynski A, Ton-That H (septembar 2006). "Type III pilus of corynebacteria: Pilus length is determined by the level of its major pilin subunit". Journal of Bacteriology. 188 (17): 6318–25. doi:10.1128/JB.00606-06. PMC 1595371. PMID 16923899.
• Rosini R, Rinaudo CD, Soriani M, Lauer P, Mora M, Maione D, Taddei A, Santi I, Ghezzo C, Brettoni C, Buccato S, Margarit I, Grandi G, Telford JL (juli 2006). "Identification of novel genomic islands coding for antigenic pilus-like structures in Streptococcus agalactiae". Molecular Microbiology. 61 (1): 126–41. doi:10.1111/j.1365-2958.2006.05225.x. PMID 16824100.
• Dramsi S, Caliot E, Bonne I, Guadagnini S, Prévost MC, Kojadinovic M, Lalioui L, Poyart C, Trieu-Cuot P (juni 2006). "Assembly and role of pili in group B streptococci". Molecular Microbiology. 60 (6): 1401–13. doi:10.1111/j.1365-2958.2006.05190.x. PMID 16796677. S2CID 40698153.
• Gaspar AH, Ton-That H (februar 2006). "Assembly of distinct pilus structures on the surface of Corynebacterium diphtheriae". Journal of Bacteriology. 188 (4): 1526–33. doi:10.1128/JB.188.4.1526-1533.2006. PMC 1367254. PMID 16452436.
• Ton-That H, Marraffini LA, Schneewind O (novembar 2004). "Protein sorting to the cell wall envelope of Gram-positive bacteria". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1694 (1–3): 269–78. doi:10.1016/j.bbamcr.2004.04.014. PMID 15546671.
• Ton-That H, Marraffini LA, Schneewind O (juli 2004). "Sortases and pilin elements involved in pilus assembly of Corynebacterium diphtheriae". Molecular Microbiology. 53 (1): 251–61. doi:10.1111/j.1365-2958.2004.04117.x. PMID 15225319.
• Ton-That H, Schneewind O (maj 2004). "Assembly of pili in Gram-positive bacteria". Trends in Microbiology. 12 (5): 228–34. doi:10.1016/j.tim.2004.03.004. PMID 15120142.
• Ton-That H, Schneewind O (novembar 2003). "Assembly of pili on the surface of Corynebacterium diphtheriae". Molecular Microbiology. 50 (4): 1429–38. doi:10.1046/j.1365-2958.2003.03782.x. PMID 14622427.

Vanjski linkovi

Ovaj članak uključuje tekst iz javnog domena Pfam i InterPro: IPR005754