N-Terminal Methionine Processing

Overview

Journal Curr Protoc Protein Sci

Specialties Biochemistry
Pathology

Date 2017 Apr 4

PMID 28369664

Citations 60

Authors

Paul T Wingfield

Affiliations

Soon will be listed here.

Abstract

Protein synthesis is initiated by methionine in eukaryotes and by formylmethionine in prokaryotes. N-terminal methionine can be co-translationally cleaved by the enzyme methionine aminopeptidase (MAP). When recombinant proteins are expressed in bacterial and mammalian expression systems, there is a simple universal rule that predicts whether the initiating methionine will be processed by MAP based on the size of the residue adjacent (penultimate) to the N-methionine. In general, if the side chains of the penultimate residues have a radius of gyration of 1.29 Å or less, methionine is cleaved. © 2017 by John Wiley & Sons, Inc.

Citing Articles

Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

Volloch V, Rits-Volloch S Genes (Basel). 2025; 16(1.

PMID: 39858593 PMC: 11764795. DOI: 10.3390/genes16010046.

Protein purification with light via a genetically encoded azobenzene side chain.

Mayrhofer P, Anneser M, Schira K, Sommer C, Theobald I, Schlapschy M Nat Commun. 2024; 15(1):10693.

PMID: 39695158 PMC: 11655525. DOI: 10.1038/s41467-024-55212-y.

Design of a yeast SUMO tag to eliminate internal translation initiation.

Law J, Gao Y, Wysocki V, Gopalan V Protein Sci. 2024; 34(1):e5256.

PMID: 39692120 PMC: 11653089. DOI: 10.1002/pro.5256.

Protein degradation kinetics measured by microinjection and live-cell fluorescence microscopy.

Vukovic D, Winkelvoss D, Kapp J, Hanny A, Burgisser H, Riermeier L Sci Rep. 2024; 14(1):27153.

PMID: 39511251 PMC: 11544240. DOI: 10.1038/s41598-024-76224-0.

Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.

Volloch V, Rits-Volloch S Int J Mol Sci. 2024; 25(18).

PMID: 39337400 PMC: 11432332. DOI: 10.3390/ijms25189913.

References

Schechter I, Berger A . On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun. 1967; 27(2):157-62. DOI: 10.1016/s0006-291x(67)80055-x. View

Helgren T, Wangtrakuldee P, Staker B, Hagen T . Advances in Bacterial Methionine Aminopeptidase Inhibition. Curr Top Med Chem. 2015; 16(4):397-414. PMC: 5009474. DOI: 10.2174/1568026615666150813145410. View

Van Valkenburgh H, Kahn R . Coexpression of proteins with methionine aminopeptidase and/or N-myristoyltransferase in Escherichia coli to increase acylation and homogeneity of protein preparations. Methods Enzymol. 2002; 344:186-93. DOI: 10.1016/s0076-6879(02)44715-5. View

Arnesen T . Towards a functional understanding of protein N-terminal acetylation. PLoS Biol. 2011; 9(5):e1001074. PMC: 3104970. DOI: 10.1371/journal.pbio.1001074. View

Liao Y, Jeng J, Wang C, Wang S, Chang S . Removal of N-terminal methionine from recombinant proteins by engineered E. coli methionine aminopeptidase. Protein Sci. 2004; 13(7):1802-10. PMC: 2279930. DOI: 10.1110/ps.04679104. View

Wang Z, Shimonaga M, Muraoka Y, Kobayashi M, Nozawa T . Methionine oxidation and its effect on the stability of a reconstituted subunit of the light-harvesting complex from Rhodospirillum rubrum. Eur J Biochem. 2001; 268(12):3375-82. DOI: 10.1046/j.1432-1327.2001.02234.x. View

Wingfield P, Graber P, Rose K, Simona M, Hughes G . Chromatofocusing of N-terminally processed forms of proteins. Isolation and characterization of two forms of interleukin-1 beta and of bovine growth hormone. J Chromatogr. 1987; 387:291-300. DOI: 10.1016/s0021-9673(01)94532-7. View

Rose K, Regamey P, Anderegg R, Wells T, Proudfoot A . Human interleukin-5 expressed in Escherichia coli has N-terminal modifications. Biochem J. 1992; 286 ( Pt 3):825-8. PMC: 1132978. DOI: 10.1042/bj2860825. View

Frottin F, Martinez A, Peynot P, Mitra S, Holz R, Giglione C . The proteomics of N-terminal methionine cleavage. Mol Cell Proteomics. 2006; 5(12):2336-49. DOI: 10.1074/mcp.M600225-MCP200. View

10.

Miller C, Strauch K, Kukral A, Miller J, Wingfield P, Mazzei G . N-terminal methionine-specific peptidase in Salmonella typhimurium. Proc Natl Acad Sci U S A. 1987; 84(9):2718-22. PMC: 304729. DOI: 10.1073/pnas.84.9.2718. View

11.

Sherman F, Stewart J, Tsunasawa S . Methionine or not methionine at the beginning of a protein. Bioessays. 1985; 3(1):27-31. DOI: 10.1002/bies.950030108. View

12.

Bonissone S, Gupta N, Romine M, Bradshaw R, Pevzner P . N-terminal protein processing: a comparative proteogenomic analysis. Mol Cell Proteomics. 2012; 12(1):14-28. PMC: 3536895. DOI: 10.1074/mcp.M112.019075. View

13.

Xiao Q, Zhang F, Nacev B, Liu J, Pei D . Protein N-terminal processing: substrate specificity of Escherichia coli and human methionine aminopeptidases. Biochemistry. 2010; 49(26):5588-99. PMC: 2906754. DOI: 10.1021/bi1005464. View

14.

Lowther W, Orville A, Madden D, Lim S, Rich D, Matthews B . Escherichia coli methionine aminopeptidase: implications of crystallographic analyses of the native, mutant, and inhibited enzymes for the mechanism of catalysis. Biochemistry. 1999; 38(24):7678-88. DOI: 10.1021/bi990684r. View

15.

Liu S, Widom J, Kemp C, Crews C, Clardy J . Structure of human methionine aminopeptidase-2 complexed with fumagillin. Science. 1998; 282(5392):1324-7. DOI: 10.1126/science.282.5392.1324. View