Related Experiment Video
Updated: Jun 6, 2026
06:16
mirMachine: A One-Stop Shop for Plant miRNA Annotation
Published on: May 1, 2021
Palmitoylation of MIR2 is required for its function.
Veronica G Anania1, Laurent Coscoy
1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
Journal of Virology
|December 17, 2010
Summary
Palmitoylation regulates Kaposi's sarcoma-associated herpesvirus (KSHV) MIR2 protein function. This modification is crucial for MIR2 to target immune proteins like MHC-I, impacting the host antiviral response.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Kaposi's sarcoma-associated herpesvirus (KSHV) encodes MIR1 and MIR2 E3 ubiquitin ligases to suppress antiviral immunity.
- MIR2 targets various cell surface proteins, many residing in lipid rafts, crucial for signal transduction.
- Palmitoylation, a lipid modification, enhances protein localization to lipid rafts.
Purpose of the Study:
- To investigate the role of palmitoylation in KSHV MIR2 E3 ligase function.
- To determine if palmitoylation affects MIR2's ability to downregulate immune substrates.
Main Methods:
- Utilized 2-bromohexadecanoic acid (2-Br) to inhibit palmitoylation.
- Performed site-directed mutagenesis on MIR2 (Cys146 to Phe).
- Assessed protein downregulation, ubiquitination, and interaction with MHC-I.
Main Results:
- 2-Br treatment inhibited MIR2-mediated downregulation of MHC-I and PECAM-1.
- Mutation of MIR2 Cys146 to Phe blocked palmitoylation and abrogated MHC-I/PECAM-1 downregulation.
- Unpalmitoylated MIR2 failed to interact with and ubiquitinate MHC-I.
- MIR2 was found to be palmitoylated in vivo during KSHV lytic infection.
Conclusions:
- Palmitoylation is essential for MIR2's ability to downregulate specific immune substrates like MHC-I and PECAM-1.
- This modification regulates MIR2 function and localization, enabling effective immune evasion during KSHV infection.
Related Concept Videos
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:39Mitochondrial Protein Sorting
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:32Lipids as Anchors
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:39Mitochondrial Precursor Proteins
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Most of the mitochondrial precursors...