Contributions of myristoylation to calcineurin structure/function

Michael T. Kennedy, Howard Brockman, Frank Rusnak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Calcineurin is a serine/threonine protein phosphatase composed of a catalytic subunit, calcineurin A (58 kDa), and a NH2-terminal myristoylated regulatory subunit, calcineurin B (19 kDa). In order to study the effect of myristoylation on calcineurin structure/function, a dual plasmid transfection system was used to generate myristoylated and nonmyristoylated calcineurin B. Both metabolic labeling of calcineurin B with radiolabeled myristic acid and electrospray mass spectral analysis confirmed that myristic acid was covalently and stoichiometrically linked to calcineurin B. Myristoyl and non- myristoyl calcineurin B were reconstituted with recombinant calcineurin A to form native-like heterodimers, and the properties of the two calcineurin forms were examined. Myristoylation had no effect on enzymatic activity, calcineurin-immunosuppressant/immunophilin interactions, or Ca2+ binding. Surprisingly, myristoylation also had no effect on calcineurin heterodimer association with phospholipid monolayers. Fatty acylation, however, significantly influenced the thermal stability of calcineurin, with an approximate 10 °C increase in t( 1/4 ) observed for myristoyl calcineurin when compared to the non-myristoyl form. Myristoylation of calcineurin B therefore appears to provide structural stability to the calcineurin heterodimer.

Original languageEnglish (US)
Pages (from-to)26517-26521
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number43
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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