Hill, B. T., Skowronski, J. (January 2005) Human N-myristoyltransferases form stable complexes with lentiviral nef and other viral and cellular substrate proteins. J Virol, 79 (2). pp. 1133-41. ISSN 0022-538X (Print)
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Abstract
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Acyl Coenzyme A metabolism Acyltransferases chemistry metabolism Amino Acid Sequence Animals COS Cells Gene Products, nef metabolism HIV-1 chemistry Humans Isoenzymes Jurkat Cells Molecular Sequence Data |
| Subjects: | bioinformatics > genomics and proteomics > annotation > sequence annotation bioinformatics > genomics and proteomics > Mapping and Rendering > Sequence Rendering organism description > virus > lentivirus |
| CSHL Authors: | |
| Communities: | CSHL labs > Skowronski lab |
| Depositing User: | CSHL Librarian |
| Date: | January 2005 |
| Date Deposited: | 12 Jan 2012 19:32 |
| Last Modified: | 03 May 2018 21:12 |
| PMCID: | PMC538564 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22594 |
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