title: Inteins, valuable genetic elements in molecular biology and biotechnology.
abstract: Inteins are internal protein elements that self-excise from their host protein and catalyze ligation of the flanking sequences (exteins) with a peptide bond. They are found in organisms in all three domains of life, and in viral proteins. Intein excision is a posttranslational process that does not require auxiliary enzymes or cofactors. This self-excision process is called protein splicing, by analogy to the splicing of RNA introns from pre-mRNA. Protein splicing involves only four intramolecular reactions, and a small number of key catalytic residues in the intein and exteins. Protein-splicing can also occur in trans. In this case, the intein is separated into N- and C-terminal domains, which are synthesized as separate components, each joined to an extein. The intein domains reassemble and link the joined exteins into a single functional protein. Understanding the cis- and trans-protein splicing mechanisms led to the development of intein-mediated protein-engineering applications, such as protein purification, ligation, cyclization, and selenoprotein production. This review summarizes the catalytic activities and structures of inteins, and focuses on the advantages of some recent intein applications in molecular biology and biotechnology.
authors.affiliation: Institute of Technical Microbiology, Technical University Hamburg-Harburg, Kasernenstr. 12, 21073, Hamburg, Germany.
authors.forename: Skander
authors.initials: S
authors.lastname: Elleuche
authors.forename: Stefanie
authors.initials: S
authors.lastname: Pöggeler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001709:Biotechnology; D002384:Catalysis; D047668:Inteins; D008967:Molecular Biology; D019154:Protein Splicing; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins
references.citation: Fungal Genet Biol. 2007 Mar;44(3):153-79
references.pmid: 17046294
references.citation: Appl Microbiol Biotechnol. 2008 Jan;77(5):1175-80
references.pmid: 17973109
references.citation: Chem Rec. 2006;6(4):183-93
references.pmid: 16900466
references.citation: Biochem Biophys Res Commun. 2007 Apr 13;355(3):830-4
references.pmid: 17316565
references.citation: Nucleic Acids Res. 2001 Sep 15;29(18):3757-74
references.pmid: 11557808
references.citation: Protein Sci. 2007 Jul;16(7):1316-28
references.pmid: 17586768
references.citation: Angew Chem Int Ed Engl. 2000 Feb;39(3):450-466
references.pmid: 10671234
references.citation: J Mol Biol. 1999 Dec 17;294(5):1327-36
references.pmid: 10600388
references.citation: Gene. 1999 Apr 29;231(1-2):1-13
references.pmid: 10231563
references.citation: J Phycol. 2008 Jun;44(3):739-50
references.pmid: 27041432
references.citation: Nat Struct Biol. 1998 Jan;5(1):31-6
references.pmid: 9437427
references.citation: J Biol Chem. 2003 Oct 3;278(40):39133-42
references.pmid: 12878593
references.citation: Nucleic Acids Res. 1994 Apr 11;22(7):1125-7
references.pmid: 8165123
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9226-31
references.pmid: 9689062
references.citation: Curr Biol. 1998 Sep 10;8(18):R634-5
references.pmid: 9740808
references.citation: Nucleic Acids Res. 1997 Mar 15;25(6):1087-93
references.pmid: 9092614
references.citation: Biopolymers. 1999;51(5):333-42
references.pmid: 10685044
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3543-8
references.pmid: 9520402
references.citation: J Biol Chem. 2010 Jan 22;285(4):2515-26
references.pmid: 19940146
references.citation: Annu Rev Microbiol. 2002;56:263-87
references.pmid: 12142479
references.citation: Trends Biochem Sci. 1995 Apr;20(4):141-2
references.pmid: 7770912
references.citation: Appl Microbiol Biotechnol. 2008 May;79(2):225-33
references.pmid: 18415096
references.citation: Adv Drug Deliv Rev. 2009 Sep 30;61(11):908-17
references.pmid: 19628015
references.citation: Protein Expr Purif. 2009 Aug;66(2):198-202
references.pmid: 19345265
references.citation: Methods. 2001 Jul;24(3):257-77
references.pmid: 11403575
references.citation: J Biol Chem. 1997 May 2;272(18):11869-73
references.pmid: 9115246
references.citation: J Biol Chem. 1997 Jun 20;272(25):15587-90
references.pmid: 9188443
references.citation: Nat Protoc. 2006;1(5):2257-62
references.pmid: 17406465
references.citation: Nucleic Acids Res. 2005 Feb 24;33(4):e34
references.pmid: 15731327
references.citation: J Biol Chem. 1998 Jun 26;273(26):16205-9
references.pmid: 9632677
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6705-10
references.pmid: 9618476
references.citation: Nat Protoc. 2007;2(5):1126-33
references.pmid: 17546003
references.citation: J Biol Chem. 1987 Dec 25;262(36):17258-9
references.pmid: 3693349
references.citation: Trends Biotechnol. 2010 Jan;28(1):37-45
references.pmid: 19897265
references.citation: Appl Environ Microbiol. 1998 Dec;64(12):4897-903
references.pmid: 9835580
references.citation: Methods Mol Biol. 2009;498:173-83
references.pmid: 18988026
references.citation: Science. 1990 Nov 2;250(4981):651-7
references.pmid: 2146742
references.citation: Protein Sci. 2005 Jun;14(6):1385-6
references.pmid: 15929993
references.citation: Mol Microbiol. 2003 Dec;50(5):1569-77
references.pmid: 14651639
references.citation: J Mol Evol. 1999 Feb;48(2):236-44
references.pmid: 9929392
references.citation: EMBO J. 1998 Feb 16;17(4):918-26
references.pmid: 9463370
references.citation: J Biol Chem. 2003 Jul 18;278(29):26315-8
references.pmid: 12766150
references.citation: Mol Biol (Mosk). 2007 Mar-Apr;41(2):314-30
references.pmid: 17514899
references.citation: Annu Rev Biochem. 2000;69:923-60
references.pmid: 10966479
references.citation: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11466-71
references.pmid: 9326633
references.citation: Adv Drug Deliv Rev. 2009 Sep 30;61(11):899-907
references.pmid: 19442693
references.citation: J Mol Biol. 2007 Mar 16;367(1):162-73
references.pmid: 17254599
references.citation: J Am Chem Soc. 2005 Aug 17;127(32):11228-9
references.pmid: 16089436
references.citation: Gene. 1997 Jun 19;192(2):271-81
references.pmid: 9224900
references.citation: Appl Microbiol Biotechnol. 2003 Jan;60(5):523-33
references.pmid: 12536251
references.citation: J Am Chem Soc. 2002 Aug 7;124(31):9044-5
references.pmid: 12148996
references.citation: J Bacteriol. 1995 May;177(9):2425-35
references.pmid: 7730274
references.citation: FEBS Lett. 2009 Mar 4;583(5):909-14
references.pmid: 19302791
references.citation: Nucleic Acids Res. 2009 May;37(8):2560-73
references.pmid: 19264795
references.citation: Microbiol Res. 2010 Oct 20;165(8):713-8
references.pmid: 20089386
references.citation: Science. 2006 Mar 17;311(5767):1563-4
references.pmid: 16543448
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1501-12
references.pmid: 19406205
references.citation: J Biotechnol. 2006 Aug 20;125(1):48-56
references.pmid: 16546284
references.citation: Gene. 1998 Jan 30;207(2):187-95
references.pmid: 9511761
references.citation: Protein Sci. 1994 Dec;3(12):2340-50
references.pmid: 7756989
references.citation: Nat Biotechnol. 1999 Nov;17(11):1112-5
references.pmid: 10545920
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13638-43
references.pmid: 10570125
references.citation: BMC Biotechnol. 2008 Oct 01;8:76
references.pmid: 18828922
references.citation: Mol Med Today. 1995 Sep;1(6):287-91
references.pmid: 9415163
references.citation: EMBO J. 2000 Sep 15;19(18):5019-26
references.pmid: 10990465
references.citation: J Nanobiotechnology. 2009 Dec 10;7:9
references.pmid: 20003264
references.citation: Biotechnol Lett. 2009 May;31(5):659-64
references.pmid: 19148582
references.citation: Curr Genet. 1994 Aug;26(2):120-5
references.pmid: 8001164
references.citation: J Mol Biol. 2006 Mar 10;356(5):1093-106
references.pmid: 16412462
references.citation: Protein Expr Purif. 2002 Dec;26(3):476-88
references.pmid: 12460773
references.citation: Annu Rev Nutr. 2003;23:17-40
references.pmid: 12524431
references.citation: FEBS Lett. 2009 May 6;583(9):1451-6
references.pmid: 19344715
references.citation: J Mol Evol. 2007 Jan;64(1):101-12
references.pmid: 17160640
references.citation: J Biol Chem. 2004 Aug 20;279(34):35281-6
references.pmid: 15194682
references.citation: J Biol Chem. 1990 Apr 25;265(12):6726-33
references.pmid: 2139027
references.citation: Trends Biotechnol. 2010 May;28(5):272-9
references.pmid: 20359761
references.citation: J Mol Biol. 1999 Oct 8;292(5):1003-16
references.pmid: 10512699
references.citation: Biotechnol Lett. 2009 Aug;31(8):1129-39
references.pmid: 19404746
references.citation: Biochemistry. 2007 Jan 9;46(1):322-30
references.pmid: 17198403
references.citation: J Biol Chem. 1999 Jun 25;274(26):18359-63
references.pmid: 10373440
references.citation: Nat Biotechnol. 2003 Mar;21(3):287-93
references.pmid: 12577068
references.citation: Nat Biotechnol. 2005 Jun;23(6):736-40
references.pmid: 15908942
references.citation: Protein Sci. 2005 Jun;14(6):1387-95
references.pmid: 15883185
references.citation: Annu Rev Genet. 2000;34:61-76
references.pmid: 11092822
references.citation: Trends Biotechnol. 2005 Jun;23(6):316-20
references.pmid: 15922084
references.citation: Biotechnol Bioeng. 2008 Oct 1;101(2):229-40
references.pmid: 18727029
references.citation: Nat Biotechnol. 1999 Sep;17(9):889-92
references.pmid: 10471931
references.citation: Annu Rev Biochem. 2000;69:447-96
references.pmid: 10966466
references.citation: Cell. 1997 Oct 3;91(1):85-97
references.pmid: 9335337
references.citation: J Mol Biol. 2005 Nov 11;353(5):1093-105
references.pmid: 16219320
references.citation: J Biol Chem. 2003 Nov 21;278(47):46826-31
references.pmid: 12975359
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11005-10
references.pmid: 19541659
references.citation: Cell. 1998 Jan 9;92(1):1-4
references.pmid: 9489693
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):383-4
references.pmid: 11752343
references.citation: Nat Protoc. 2007;2(5):1225-35
references.pmid: 17546018
references.citation: Appl Microbiol Biotechnol. 2006 Oct;72(5):959-67
references.pmid: 16544141