title: Recent advances in segmental isotope labeling of proteins: NMR applications to large proteins and glycoproteins.
abstract: In the last 15 years substantial advances have been made to place isotope labels in native and glycosylated proteins for NMR studies and structure determination. Key developments include segmental isotope labeling using Native Chemical Ligation, Expressed Protein Ligation and Protein Trans-Splicing. These advances are pushing the size limit of NMR spectroscopy further making larger proteins accessible for this technique. It is just emerging that segmental isotope labeling can be used to define inter-domain interactions in NMR structure determination. Labeling of post-translational modified proteins like glycoproteins remains difficult but some promising developments were recently achieved. Key achievements are segmental and site-specific labeling schemes that improve resonance assignment and structure determination of the glycan moiety. We adjusted the focus of this perspective article to concentrate on the NMR applications based on recent developments rather than on labeling methods themselves to illustrate the considerable potential for biomolecular NMR.
authors.affiliation: Institute for Molecular Biology and Biophysics, ETH Zürich, Zurich, Switzerland.
authors.forename: Lenka
authors.initials: L
authors.lastname: Skrisovska
authors.forename: Mario
authors.initials: M
authors.lastname: Schubert
authors.forename: Frédéric H-T
authors.initials: FH
authors.lastname: Allain
mesh_terms: D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D007553:Isotope Labeling / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D011506:Proteins
references.citation: Protein Expr Purif. 2000 Aug;19(3):335-42
references.pmid: 10910722
references.citation: Gene. 1998 Jan 30;207(2):187-95
references.pmid: 9511761
references.citation: J Biotechnol. 2008 Apr 30;134(3-4):261-5
references.pmid: 18378033
references.citation: Science. 1995 Sep 1;269(5228):1273-8
references.pmid: 7544493
references.citation: Methods Mol Biol. 2004;278:17-33
references.pmid: 15317988
references.citation: Chem Rev. 2009 Jan;109(1):131-63
references.pmid: 19093879
references.citation: J Am Chem Soc. 2005 May 4;127(17):6198-206
references.pmid: 15853324
references.citation: Biochemistry. 1999 Jun 29;38(26):8377-84
references.pmid: 10387083
references.citation: Glycobiology. 1994 Aug;4(4):485-9
references.pmid: 7827410
references.citation: EMBO J. 2000 Jun 15;19(12):3132-41
references.pmid: 10856256
references.citation: Gene. 1999 Apr 29;231(1-2):1-13
references.pmid: 10231563
references.citation: FEBS Lett. 1993 Aug 9;328(1-2):49-54
references.pmid: 8344434
references.citation: Chembiochem. 2006 Feb;7(2):359-65
references.pmid: 16381046
references.citation: Chem Rev. 2002 Dec;102(12):4869-84
references.pmid: 12475209
references.citation: In Vitro Cell Dev Biol. 1986 Jul;22(7):363-8
references.pmid: 3733634
references.citation: Glycobiology. 2004 Nov;14(11):999-1009
references.pmid: 15215231
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9226-31
references.pmid: 9689062
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3543-8
references.pmid: 9520402
references.citation: EMBO J. 2006 May 3;25(9):1957-66
references.pmid: 16619027
references.citation: Biochemistry. 1991 Jan 8;30(1):270-8
references.pmid: 1899019
references.citation: Magn Reson Chem. 2005 Oct;43(10):805-15
references.pmid: 15996005
references.citation: Eur J Biochem. 2004 Feb;271(4):663-77
references.pmid: 14764082
references.citation: Science. 2002 Nov 29;298(5599):1790-3
references.pmid: 12459590
references.citation: Bioorg Med Chem. 2001 Sep;9(9):2479-84
references.pmid: 11553489
references.citation: Proteomics. 2004 Jan;4(1):226-34
references.pmid: 14730684
references.citation: Methods. 2001 Jul;24(3):257-77
references.pmid: 11403575
references.citation: Protein Sci. 1998 Nov;7(11):2256-64
references.pmid: 9827992
references.citation: Methods Enzymol. 2001;339:238-58
references.pmid: 11462814
references.citation: Annu Rev Biochem. 2003;72:249-89
references.pmid: 12626339
references.citation: EMBO J. 2006 Jan 11;25(1):150-62
references.pmid: 16362043
references.citation: J Am Chem Soc. 2004 Dec 22;126(50):16632-8
references.pmid: 15600369
references.citation: J Biol Chem. 1998 Jun 26;273(26):16205-9
references.pmid: 9632677
references.citation: Chem Rev. 2002 Feb;102(2):371-86
references.pmid: 11841247
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6705-10
references.pmid: 9618476
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10068-73
references.pmid: 10468563
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12366-71
references.pmid: 9356455
references.citation: J Am Chem Soc. 2008 Apr 30;130(17):5618-9
references.pmid: 18393418
references.citation: J Biomol NMR. 1998 Oct;12(3):385-94
references.pmid: 9835046
references.citation: Biochemistry. 1999 Dec 7;38(49):16040-4
references.pmid: 10587426
references.citation: FEBS Lett. 1999 Oct 8;459(2):166-72
references.pmid: 10518012
references.citation: J Mol Biol. 2008 Jan 4;375(1):151-64
references.pmid: 17936301
references.citation: Biochemistry. 1996 Jul 9;35(27):8815-23
references.pmid: 8688417
references.citation: Nat Struct Biol. 1997 Jul;4(7):527-31
references.pmid: 9228944
references.citation: EMBO J. 1998 Feb 16;17(4):918-26
references.pmid: 9463370
references.citation: Cell. 2002 Nov 15;111(4):565-76
references.pmid: 12437929
references.citation: Bioorg Med Chem. 2005 Feb 1;13(3):909-15
references.pmid: 15653356
references.citation: J Biomol NMR. 2001 May;20(1):11-4
references.pmid: 11430750
references.citation: J Biomol NMR. 2004 Jan;28(1):59-67
references.pmid: 14739639
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12694-9
references.pmid: 14557549
references.citation: Biopolymers. 1994 Oct;34(10):1327-38
references.pmid: 7948719
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: Nat Methods. 2006 Jun;3(6):429-38
references.pmid: 16721376
references.citation: Biochemistry. 2007 Sep 18;46(37):10722-32
references.pmid: 17715945
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11557-61
references.pmid: 17609375
references.citation: Methods Mol Biol. 2003;205:43-68
references.pmid: 12491879
references.citation: J Am Chem Soc. 2008 Sep 10;130(36):11864-5
references.pmid: 18700760
references.citation: Curr Opin Biotechnol. 2002 Aug;13(4):297-303
references.pmid: 12323349
references.citation: Glycobiology. 1999 Feb;9(2):125-31
references.pmid: 9949190
references.citation: J Biomol NMR. 1996 Jun;7(4):295-304
references.pmid: 8765736
references.citation: J Biol Chem. 2005 Sep 2;280(35):31019-26
references.pmid: 15983037
references.citation: J Biol Chem. 1982 Feb 25;257(4):1829-35
references.pmid: 7056747
references.citation: Biochim Biophys Acta. 2006 Apr;1760(4):693-700
references.pmid: 16343775
references.citation: J Am Chem Soc. 2008 Jan 16;130(2):501-10
references.pmid: 18085777
references.citation: Biochemistry. 1991 Jul 2;30(26):6604-10
references.pmid: 2054358
references.citation: Chembiochem. 2008 Dec 15;9(18):2958-61
references.pmid: 19031436
references.citation: Cell. 2003 Dec 12;115(6):739-50
references.pmid: 14675538
references.citation: J Am Chem Soc. 2004 Mar 3;126(8):2439-46
references.pmid: 14982452
references.citation: Curr Opin Chem Biol. 2006 Oct;10(5):509-19
references.pmid: 16905354
references.citation: FEBS Lett. 1994 Aug 15;350(1):87-90
references.pmid: 8062930
references.citation: Angew Chem Int Ed Engl. 2009;48(33):6128-31
references.pmid: 19591176
references.citation: Annu Rev Biophys Biomol Struct. 1998;27:357-406
references.pmid: 9646872
references.citation: J Biomol NMR. 2003 Mar;25(3):235-42
references.pmid: 12652135
references.citation: Chem Biol. 2000 Apr;7(4):253-61
references.pmid: 10780925
references.citation: Angew Chem Int Ed Engl. 2009;48(11):1936-40
references.pmid: 19173366
references.citation: Science. 1994 Nov 4;266(5186):776-9
references.pmid: 7973629
references.citation: Protein Sci. 2007 Sep;16(9):2056-64
references.pmid: 17660260
references.citation: Biochim Biophys Acta. 2008 Mar;1780(3):619-25
references.pmid: 18157953
references.citation: J Biol Chem. 2007 Jul 27;282(30):22228-38
references.pmid: 17553784
references.citation: J Bacteriol. 1997 Oct;179(20):6378-82
references.pmid: 9335286
references.citation: J Biomol NMR. 2006 Dec;36(4):225-33
references.pmid: 17063379
references.citation: Curr Opin Chem Biol. 2006 Dec;10(6):638-44
references.pmid: 17046315
references.citation: Structure. 1994 Mar 15;2(3):185-99
references.pmid: 7520819
references.citation: Eur J Biochem. 1996 Oct 1;241(1):229-42
references.pmid: 8898911
references.citation: FASEB J. 2008 Dec;22(12):4055-66
references.pmid: 18714070
references.citation: J Biomol NMR. 1999 Feb;13(2):149-59
references.pmid: 10070756
references.citation: Nat Biotechnol. 2005 Jun;23(6):736-40
references.pmid: 15908942
references.citation: Glycoconj J. 2008 Apr;25(3):245-57
references.pmid: 18274893
references.citation: J Mol Biol. 1994 Feb 11;236(1):300-9
references.pmid: 8107111
references.citation: J Biomol NMR. 1993 Jul;3(4):429-41
references.pmid: 8400831
references.citation: Biochemistry. 2007 May 8;46(18):5579-85
references.pmid: 17439157
references.citation: Biochemistry. 2000 May 23;39(20):6012-21
references.pmid: 10821673
references.citation: Science. 2005 Sep 23;309(5743):2054-7
references.pmid: 16179478
references.citation: Biopolymers. 1999;51(5):343-54
references.pmid: 10685045
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8536-41
references.pmid: 12084914
references.citation: Annu Rev Biochem. 2000;69:447-96
references.pmid: 10966466
references.citation: Nat Struct Biol. 2000 Mar;7(3):200-4
references.pmid: 10700277
references.citation: Curr Opin Biotechnol. 2005 Aug;16(4):440-6
references.pmid: 16026977
references.citation: Glycobiology. 1993 Apr;3(2):97-130
references.pmid: 8490246
references.citation: J Biomol NMR. 2000 Dec;18(4):357-60
references.pmid: 11200530
references.citation: Science. 2006 Nov 17;314(5802):1148-50
references.pmid: 17110579
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):388-93
references.pmid: 9892643
references.citation: J Am Chem Soc. 2003 Aug 27;125(34):10420-8
references.pmid: 12926967
references.citation: Biochim Biophys Acta. 1999 Dec 6;1473(1):4-8
references.pmid: 10580125
references.citation: Methods Enzymol. 2001;338:305-19
references.pmid: 11460555
references.citation: J Biomol NMR. 2009 Mar;43(3):145-50
references.pmid: 19140010
references.citation: Science. 1994 Oct 14;266(5183):243-7
references.pmid: 7939659
references.citation: Angew Chem Int Ed Engl. 2002 Jun 17;41(12):2171-4
references.pmid: 19746634
references.citation: J Am Chem Soc. 2009 Jan 28;131(3):1274-81
references.pmid: 19154179
references.citation: Biochemistry. 1993 Oct 19;32(41):10995-1006
references.pmid: 8105887