Treffer: Genetic code expansion and enzymatic modifications as accessible methods for studying site-specific post-translational modifications of alpha-synuclein and tau.
Title:
Genetic code expansion and enzymatic modifications as accessible methods for studying site-specific post-translational modifications of alpha-synuclein and tau.
Authors:
Saleh IG; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Shimogawa M; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Ramirez J; Graduate Group in Biochemistry, Biophysics, and Chemical Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Abakah B; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Venkatesh Y; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., James HP; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Li MH; Department of Biochemistry, Weill Cornell Medicine, New York, New York, USA., Louie SA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA., Lougee MG; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Chia WK; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Brue C; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Cooley RB; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA., Mehl RA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA., Baumgart T; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Mach RH; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Eliezer D; Department of Biochemistry, Weill Cornell Medicine, New York, New York, USA., Rhoades E; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Petersson EJ; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Source:
Protein science : a publication of the Protein Society [Protein Sci] 2025 Oct; Vol. 34 (10), pp. e70302.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9211750 Publication Model: Print Cited Medium: Internet ISSN: 1469-896X (Electronic) Linking ISSN: 09618368 NLM ISO Abbreviation: Protein Sci Subsets: MEDLINE
Imprint Name(s):
Publication: 2001- : Woodbury, NY : Cold Spring Harbor Laboratory Press
Original Publication: New York, N.Y. : Cambridge University Press, c1992-
Original Publication: New York, N.Y. : Cambridge University Press, c1992-
MeSH Terms:
Comments:
Update of: bioRxiv. 2025 May 17:2025.05.16.654576. doi: 10.1101/2025.05.16.654576.. (PMID: 40463212)
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J Neurochem. 2000 Apr;74(4):1587-95. (PMID: 10737616)
Chem Rev. 2024 Nov 13;124(21):11962-12005. (PMID: 39466033)
Chembiochem. 2021 Apr 16;22(8):1440-1447. (PMID: 33274519)
Mol Biol Cell. 2013 Jun;24(11):1649-60, S1-3. (PMID: 23576548)
Biophys J. 2003 Feb;84(2 Pt 1):750-6. (PMID: 12547759)
Nature. 2011 Apr 28;472(7344):499-503. (PMID: 21478873)
J Am Chem Soc. 2018 May 30;140(21):6611-6621. (PMID: 29684271)
Protein Sci. 2025 Oct;34(10):e70302. (PMID: 40944447)
Nat Chem Biol. 2008 Apr;4(4):232-4. (PMID: 18278036)
Biophys J. 2006 Jun 15;90(12):4692-700. (PMID: 16581836)
Annu Rev Neurosci. 2001;24:1121-59. (PMID: 11520930)
J Biol Chem. 2018 Jul 6;293(27):10744-10756. (PMID: 29773654)
ACS Chem Biol. 2016 Sep 16;11(9):2428-37. (PMID: 27356045)
ACS Chem Neurosci. 2018 Nov 21;9(11):2521-2527. (PMID: 29750499)
J Neurochem. 2000 Jul;75(1):436-9. (PMID: 10854289)
Neuron. 2010 Sep 23;67(6):953-66. (PMID: 20869593)
Sci Rep. 2016 Mar 04;6:22685. (PMID: 26940749)
PLoS One. 2010 Dec 23;5(12):e15801. (PMID: 21203426)
Curr Opin Chem Biol. 2021 Oct;64:76-89. (PMID: 34175787)
Nat Chem Biol. 2017 Dec;13(12):1253-1260. (PMID: 29035361)
Org Biomol Chem. 2016 Feb 7;14(5):1584-92. (PMID: 26695131)
J Proteomics. 2022 Feb 10;252:104432. (PMID: 34818585)
Methods. 2023 Oct;218:101-109. (PMID: 37549799)
Nat Neurosci. 2023 Feb;26(2):213-225. (PMID: 36690898)
Lancet Public Health. 2022 Feb;7(2):e105-e125. (PMID: 34998485)
ACS Chem Biol. 2019 Jul 19;14(7):1564-1572. (PMID: 31243963)
BMB Rep. 2018 Jun;51(6):265-273. (PMID: 29661268)
J Neurosci. 2002 Oct 15;22(20):8797-807. (PMID: 12388586)
Nat Commun. 2022 Aug 6;13(1):4586. (PMID: 35933508)
Pharmacol Rev. 2024 Oct 16;76(6):1254-1290. (PMID: 39164116)
ACS Cent Sci. 2021 Dec 22;7(12):1986-1995. (PMID: 34963892)
Science. 2010 Sep 24;329(5999):1663-7. (PMID: 20798282)
Cell. 2022 Oct 13;185(21):3913-3930.e19. (PMID: 36198316)
Science. 2018 Jun 15;360(6394):1242-1246. (PMID: 29748322)
Hum Mol Genet. 2014 Jun 1;23(11):2858-79. (PMID: 24412932)
J Am Chem Soc. 2015 Feb 11;137(5):1734-7. (PMID: 25625321)
J Neurosci. 1996 Sep 15;16(18):5583-92. (PMID: 8795614)
Nat Commun. 2011;2:252. (PMID: 21427723)
J Biol Chem. 2022 Dec;298(12):102613. (PMID: 36265582)
Chem Rev. 2024 May 22;124(10):6592-6642. (PMID: 38691379)
Chem Sci. 2020 Sep 10;11(47):12746-12754. (PMID: 33889379)
Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20305-20315. (PMID: 32737160)
J Mol Biol. 2022 Dec 15;434(23):167859. (PMID: 36270580)
Biochem Biophys Res Commun. 2014 Jan 17;443(3):1085-91. (PMID: 24380864)
J Clin Invest. 2016 Aug 1;126(8):2970-88. (PMID: 27348587)
Chem Sci. 2015 Jan 1;6(1):50-69. (PMID: 28553457)
Nat Commun. 2024 Mar 27;15(1):2677. (PMID: 38538591)
Front Neurol. 2021 Jan 07;11:595532. (PMID: 33488497)
Angew Chem Int Ed Engl. 2013 Jun 10;52(24):6210-3. (PMID: 23629972)
Biomolecules. 2023 Oct 02;13(10):. (PMID: 37892158)
PLoS One. 2024 Sep 10;19(9):e0309416. (PMID: 39255305)
Grant Information:
RF1-NS103873 United States NH NIH HHS; U19-NS110456 United States NH NIH HHS; RF1 NS125770 United States NS NINDS NIH HHS; RF1 NS103873 United States NS NINDS NIH HHS; T32-GM133398 United States NH NIH HHS; Nakajima Foundation; T32-AG000255 United States NH NIH HHS; RM1 GM144227 United States GM NIGMS NIH HHS; RF-1NS125770 United States NH NIH HHS; S10-OD030460 United States NH NIH HHS; T32 GM133398 United States GM NIGMS NIH HHS; U19 NS110456 United States NS NINDS NIH HHS; T32 AG000255 United States AG NIA NIH HHS; R01-GM097552 United States NH NIH HHS; R01 NS103873 United States NS NINDS NIH HHS; R01 GM097552 United States GM NIGMS NIH HHS; S10 OD030460 United States OD NIH HHS; RM1-GM144227 United States NH NIH HHS; U19 AG062418 United States AG NIA NIH HHS; R01 NS125770 United States NS NINDS NIH HHS; CHE-1827457 NSF
Contributed Indexing:
Keywords: alpha‐synuclein; genetic code expansion; post‐translational modification; tau
Substance Nomenclature:
0 (alpha-Synuclein)
0 (tau Proteins)
0 (tau Proteins)
Entry Date(s):
Date Created: 20250913 Date Completed: 20250916 Latest Revision: 20250920
Update Code:
20250920
PubMed Central ID:
PMC12432407
DOI:
10.1002/pro.70302
PMID:
40944447
Database:
MEDLINE
Weitere Informationen
Alpha-synuclein (αS) and tau play important roles in the pathology of Parkinson's disease and Alzheimer's disease, respectively, as well as numerous other neurodegenerative diseases. Both proteins are classified as intrinsically disordered proteins (IDPs), as they have no stable structure that underlies their function in healthy tissue, and both proteins are prone to aggregation in disease states. There is substantial interest in understanding the roles that post-translational modifications (PTMs) play in regulating the structural dynamics and function of αS and tau monomers, as well as their propensity to aggregate. While there have been many valuable insights into site-specific effects of PTMs garnered through chemical synthesis and semi-synthesis, these techniques are often outside of the expertise of biochemistry and biophysics laboratories wishing to study αS and tau. Therefore, we have assembled a primer on genetic code expansion and enzymatic modification approaches to installing PTMs into αS and tau site-specifically, including isotopic labeling for NMR and fluorescent labeling for biophysics and microscopy experiments. These methods should be enabling for those wishing to study authentic PTMs in αS or tau as well as the broader field of IDPs and aggregating proteins.
(© 2025 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)