This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hill, B. T.
Right arrow Articles by Skowronski, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hill, B. T.
Right arrow Articles by Skowronski, J.

 Previous Article  |  Next Article 

Journal of Virology, January 2005, p. 1133-1141, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1133-1141.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human N-Myristoyltransferases Form Stable Complexes with Lentiviral Nef and Other Viral and Cellular Substrate Proteins

Brian T. Hill{dagger} and Jacek Skowronski*

Cold Spring Harbor Laboratory, Cold Spring Harbor, and Program in Genetics and Medical Scientist Training Program, Stony Brook University, Stony Brook, New York

Received 27 June 2004/ Accepted 26 August 2004

Nef is a multifunctional virulence factor of primate lentiviruses that facilitates viral replication in the infected host. All known functions of Nef require that it be myristoylated at its N terminus. This reaction is catalyzed by N-myristoyltransferases (NMTs), which transfer myristate from myristoyl coenzyme A (myristoyl-CoA) to the N-terminal glycine of substrate proteins. Two NMT isoforms (NMT-1 and NMT-2) are expressed in mammalian cells. To provide a better mechanistic understanding of Nef function, we used biochemical and microsequencing techniques to isolate and identify Nef-associated proteins. Through these studies, NMT-1 was identified as an abundant Nef-associated protein. The Nef-NMT-1 complex is most likely a transient intermediate of the myristoylation reaction of Nef and is modulated by agents which affect the size of the myristoyl-CoA pool in the cell. We also examined two other proteins that bear an N-terminal myristoylation signal, human immunodeficiency virus type 1 Gag and Hck protein tyrosine kinase, and found that Gag bound preferentially the NMT-2 isoform, while Hck bound mostly to NMT-1. Recognition of different NMT isoforms by these viral and cellular substrate proteins suggests nonoverlapping roles for these enzymes in vivo and reveals a potential for the development of inhibitors that target the myristoylation of specific viral substrates more selectively.

* Corresponding author. Mailing address: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. Phone: (516) 367-8407. Fax: (516) 367-8454. E-mail: skowrons{at}cshl.org.

{dagger} Present address: Pritzker School of Medicine, University of Chicago, Chicago, IL 60637.

Journal of Virology, January 2005, p. 1133-1141, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1133-1141.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Seaton, K. E., Smith, C. D. (2008). N-Myristoyltransferase isozymes exhibit differential specificity for human immunodeficiency virus type 1 Gag and Nef. J. Gen. Virol. 89: 288-296 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»