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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Volume 390, Issue 11 (Nov 2009)


Protein carboxyl methylation and the biochemistry of memory

Zhu Li
  • Signum Biosciences, Inc., Monmouth Junction, NJ 08852, USA
/ Jeffry B. Stock
  • Signum Biosciences, Inc., Monmouth Junction, NJ 08852, USA
  • Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
Published Online: 2009-09-13 | DOI: https://doi.org/10.1515/BC.2009.133


Bacterial chemotaxis is mediated by two reversible protein modification chemistries: phosphorylation and carboxyl methylation. Attractants bind to membrane chemoreceptors that control the activity of a protein kinase which acts in turn to control flagellar motor activity. Coordinate changes in receptor carboxyl methylation provide a negative feedback mechanism that serves a memory function. Protein carboxyl methylation might play an analogous role in the nervous system. Two protein carboxyl methyltransferases serve to regulate signal transduction pathways in eukaryotic cells. One is highly expressed in the Purkinje layer of the cerebellum where it methyl esterifies prenylated cysteine residues at the carboxyl-termini of Ras-related and heterotrimeric G-proteins. The other is abundant throughout the brain where it methylates the carboxyl-terminus of protein phosphatase 2A. The phosphatase methyltransferase and the protein methylesterase that reverses phosphatase methylation are structurally related to the corresponding bacterial chemotaxis methylating and demethylating enzymes. Recent results indicate that deficiencies in phosphatase methylation play an important role in the etiology of Alzheimer's disease.

Keywords: Alzheimer's disease; chemotaxis; G-protein; isoprenylcysteine methyltransferase (ICMT); protein phosphatase 2A (PP2A); S-adenosylmethionine

About the article

Corresponding author

Received: 2009-06-05

Accepted: 2009-08-26

Published Online: 2009-09-13

Published in Print: 2009-11-01

Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2009.133. Export Citation

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