The matrix domain (MA) of human immunodeficiency virus type 1 Pr55Gag is covalently modified with a myristoyl group that mediates efficient viral production. However, the role of myristoylation, particularly in the viral entry process, remains uninvestigated. This study replaced the myristoylation signal of MA with a well-studied phosphatidylinositol 4,5-biphosphate-binding plasma membrane (PM) targeting motif, the phospholipase C-delta1 pleckstrin homology (PH) domain. PH-Gag-Pol PM targeting and viral production efficiencies were improved compared with Gag-Pol, consistent with the estimated increases in Gag-PM affinity. Both virions were recovered in similar sucrose density-gradient fractions and had similar mature virion morphologies. Importantly, PH-Gag-Pol and Gag-Pol pseudovirions had almost identical infectivity, suggesting a dispensable role for myristoylation in the virus life cycle. PH-Gag-Pol might be useful in separating the myristoylation-dependent processes from the myristoylation-independent processes. This the first report demonstrating infectious pseudovirion production without myristoylated Pr55Gag.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885030PMC
http://dx.doi.org/10.1099/vir.0.2008/004820-0DOI Listing

Publication Analysis

Top Keywords

myristoylation signal
8
human immunodeficiency
8
immunodeficiency virus
8
virus type
8
type pr55gag
8
phospholipase c-delta1
8
c-delta1 pleckstrin
8
pleckstrin homology
8
homology domain
8
infectious pseudovirion
8

Similar Publications

Refining minimal engineered receptors for specific activation of on-target signaling molecules.

Sci Rep

December 2024

Laboratory of Cell Vaccine, Microbial Research Center for Health and Medicine (MRCHM), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki-Shi, Osaka, 567-0085, Japan.

Since designer cells are attracting much attention as a new modality in gene and cell therapy, it would be advantageous to develop synthetic receptors that recognize artificial ligands and activate solely signaling molecules of interest. In this study, we refined the construction of our previously developed minimal engineered receptors (MERs) to avoid off-target activation of STAT5 while maintaining on-target activation of signaling molecules corresponding to tyrosine motifs. Among the myristoylated, cytoplasmic, and transmembrane types of MERs, the cytoplasmic type had the highest signaling efficiency, although there was off-target activation of STAT5 upon ligand stimulation.

View Article and Find Full Text PDF

Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.

View Article and Find Full Text PDF

Marcks overexpression in retinal ganglion cells promotes optic nerve regeneration.

Cell Death Dis

December 2024

Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Regeneration of injured central nervous system (CNS) axons is highly restricted, leading to permanent neurological deficits. The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells, plays critical roles in development, brain plasticity, and tissues regeneration. However, little is known about the role of Marcks in CNS axon regeneration.

View Article and Find Full Text PDF

In vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), phosphatidylinositol 4,5-bisphosphate (PIP) acts as a substrate for phospholipase C (PLC)- and phosphoinositol 3-kinase (PI3K)-mediated signaling pathways and an unmodified ligand at ion channels and other macromolecules, which are key processes in the regulation of cell physiological and pathological phenotypes. It is envisaged that these distinct roles of PIP are achieved by PIP-binding proteins, which act as PIP buffers to produce discrete pools of PIP that permits targeted release within the cell. This review discusses evidence for the expression, cell distribution, and role of myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP-binding protein, in cellular signaling and function of VSMCs.

View Article and Find Full Text PDF

Marcks and Marcksl1 are abundant proteins that shuttle between the cytoplasm and membrane to modulate multiple cellular processes, including cytoskeletal dynamics, proliferation, and secretion. Here, we performed loss- and gain-of-function experiments in to reveal the novel roles of these proteins in spinal cord development and regeneration. We show that Marcks and Marcksl1 have partly redundant functions and are required for normal neurite formation and proliferation of neuro-glial progenitors during embryonic spinal cord development and for its regeneration during tadpole stages.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!