M04
目录号 : GC49673
A STING agonist
Cas No.:875158-73-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
M04 is an agonist of stimulator of interferon genes (STING).1 It induces IFN reporter gene expression in HEK293T cells expressing wild-type human STING but not in HEK293T cells expressing the R71H-G230A-R293Q (HAQ) human STING variant nor in mouse RAW 264.7 cells, indicating allelic- and species-dependent activities, at 75 µM. M04 induces the production of TNF-α, IL-10, IL-1β, and IL-12p70 in human peripheral blood mononuclear cells (PBMCs). It increases the percentage of isolated human monocyte-derived dendritic cells expressing the MHC class II cell surface receptor HLA-DR and the co-stimulatory molecules CD40, CD80, and CD86, as well as increases T cell cross-priming of the same cells in an ex vivo assay, when used at a concentration of 50 µM.
1.Abraham, J., Botto, S., Mizuno, N., et al.Characterization of a novel compound that stimulates STING-mediated innate immune activity in an allele-specific mannerFront. Immunol.111430(2020)
| Cas No. | 875158-73-9 | SDF | Download SDF |
| Canonical SMILES | O=S(C1=CC=C(C)C=C1)(C2=C(N(C)C)SC(S(=O)(C3CCCCC3)=O)=N2)=O | ||
| 分子式 | C18H24N2O4S3 | 分子量 | 428.6 |
| 溶解度 | Chloroform: soluble | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3332 mL | 11.6659 mL | 23.3318 mL |
| 5 mM | 0.4666 mL | 2.3332 mL | 4.6664 mL |
| 10 mM | 0.2333 mL | 1.1666 mL | 2.3332 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The structure of the cytomegalovirus-encoded M04 glycoprotein, a prototypical member of the m02 family of immunoevasins
J Biol Chem 2014 Aug 22;289(34):23753-63.PMID:24982419DOI:10.1074/jbc.M114.584128.
The ability of CMVs to evade the immune system of the host is dependent on the expression of a wide array of glycoproteins, many of which interfere with natural killer cell function. In murine CMV, two large protein families mediate this immune-evasive function. Although it is established that the m145 family members mimic the structure of MHC-I molecules, the structure of the m02 family remains unknown. The most extensively studied m02 family member is M04, a glycoprotein that escorts newly assembled MHC-I molecules to the cell surface, presumably to avoid "missing self" recognition. Here we report the crystal structure of the M04 ectodomain, thereby providing insight into this large immunoevasin family. M04 adopted a β-sandwich immunoglobulin variable (Ig-V)-like fold, despite sharing very little sequence identity with the Ig-V superfamily. In addition to the Ig-V core, M04 possesses several unique structural features that included an unusual β-strand topology, a number of extended loops and a prominent α-helix. The M04 interior was packed by a myriad of hydrophobic residues that form distinct clusters around two conserved tryptophan residues. This hydrophobic core was well conserved throughout the m02 family, thereby indicating that murine CMV encodes a number of Ig-V-like molecules. We show that M04 binds a range of MHC-I molecules with low affinity in a peptide-independent manner. Accordingly, the structure of M04, which represents the first example of an murine CMV encoded Ig-V fold, provides a basis for understanding the structure and function of this enigmatic and large family of immunoevasins.
Positive Role of the MHC Class-I Antigen Presentation Regulator M04/gp34 of Murine Cytomegalovirus in Antiviral Protection by CD8 T Cells
Front Cell Infect Microbiol 2020 Aug 26;10:454.PMID:32984075DOI:10.3389/fcimb.2020.00454.
Murine cytomegalovirus (mCMV) codes for MHC class-I trafficking modulators M04/gp34, m06/gp48, and m152/gp40. By interacting with the MHC class-Iα chain, these proteins disconnect peptide-loaded MHC class-I (pMHC-I) complexes from the constitutive vesicular flow to the cell surface. Based on the assumption that all three inhibit antigen presentation, and thus the recognition of infected cells by CD8 T cells, they were referred to as "immunoevasins." Improved antigen presentation mediated by M04 in the presence of m152 after infection with deletion mutant mCMV-Δm06W, compared to mCMV-Δm04m06 expressing only m152, led us to propose renaming these molecules "viral regulators of antigen presentation" (vRAP) to account for both negative and positive functions. In accordance with a positive function, m04-pMHC-I complexes were found to be displayed on the cell surface, where they are primarily known as ligands for Ly49 family natural killer (NK) cell receptors. Besides the established role of M04 in NK cell silencing or activation, an anti-immunoevasive function by activation of CD8 T cells is conceivable, because the binding site of M04 to MHC class-Iα appears not to mask the peptide binding site for T-cell receptor recognition. However, functional evidence was based on mCMV-Δm06W, a virus of recently doubted authenticity. Here we show that mCMV-Δm06W actually represents a mixture of an authentic m06 deletion mutant and a mutant with an accidental additional deletion of a genome region encompassing also gene m152. Reanalysis of previously published experiments for the authentic mutant in the mixture confirms the previously concluded positive vRAP function of M04.
Ly49P recognition of cytomegalovirus-infected cells expressing H2-Dk and CMV-encoded M04 correlates with the NK cell antiviral response
J Exp Med 2009 Mar 16;206(3):515-23.PMID:19255146DOI:10.1084/jem.20080954.
Natural killer (NK) cells are crucial in resistance to certain viral infections, but the mechanisms used to recognize infected cells remain largely unknown. Here, we show that the activating Ly49P receptor recognizes cells infected with mouse cytomegalovirus (MCMV) by a process that requires the presence of H2-D(k) and the MCMV M04 protein. Using H2 chimeras between H2-D(b) and -D(k), we demonstrate that the H2-D(k) peptide-binding platform is required for Ly49P recognition. We identified M04 as a viral component necessary for recognition using a panel of MCMV-deletion mutant viruses and complementation of m04-deletion mutant (Deltam04) virus infection. MA/My mice, which express Ly49P and H2-D(k), are resistant to MCMV; however, infection with Deltam04 MCMV abrogates resistance. Depletion of NK cells in MA/My mice abrogates their resistance to wild-type MCMV infection, but does not significantly affect viral titers in mice infected with Deltam04 virus, implicating NK cells in host protection through m04-dependent recognition. These findings reveal a novel mechanism of major histocompatibility complex class I-restricted recognition of virally infected cells by an activating NK cell receptor.
Recessive embryonic lethal mutations uncovered in heterozygous condition in silkworm semiconsomic strains
Insect Biochem Mol Biol 2023 Apr;155:103933.PMID:36931352DOI:10.1016/j.ibmb.2023.103933.
In this study, we found two embryonic lethal mutations, t04 lethal (l-t04) and M04 lethal (l-m04), in semiconsomic strains T04 and M04, respectively. In these semiconsomic strains, the entire diploid genome, except for one chromosome 4 of the wild silkworm Bombyx mandarina, is substituted with chromosomes of the domesticated silkworm B. mori, and l-t04 and l-m04 mutations are located on B. mandarina-derived chromosome 4. To clarify the cause of the lethalities and the genes responsible for these mutations, positional cloning and CRISPR/Cas9 mediated knockout screening were performed. Finally, genetic complementation tests identified the mutations responsible for the l-t04 and l-m04 as the Bombyx homolog of imaginal discs arrested (Bmida) and TATA box binding protein-associated factor 5 (BmTaf5), respectively. Lethal stages of each knockout mutant indicated the importance of these genes in B. mori late embryogenesis. The lethal mutations responsible for l-t04 and l-m04 were not found in parental strains or wild B. mandarina collected from 39 distinct locations in Japan, indicating that both mutations were independently introduced during or after the development of the semiconsomic strains. We conclude that the recessive embryonic lethality in the T04 and M04 strains is due to deleterious mutations produced in B. mandarina-derived chromosome 4.
The putative natural killer decoy early gene M04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells
J Virol 2000 Feb;74(4):1871-84.PMID:10644360DOI:10.1128/jvi.74.4.1871-1884.2000.
Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the "missing self." The retention, however, is counteracted by the M04 early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 might serve to silence NK cells and thereby complete the immune evasion of MCMV. In light of these current views, we provide here results demonstrating an in vivo role for gp34 in protective antiviral immunity. We have identified an antigenic nonapeptide derived from gp34 and presented by the MHC-I molecule D(d). Besides the immunodominant immediate-early nonapeptide consisting of IE1 amino acids 168-176 (IE1(168-176)), the early nonapeptide M04(243-251) is the second antigenic peptide described for MCMV. The primary immune response to MCMV generates significant m04-specific CD8 T-cell memory. Upon adoptive transfer into immunodeficient recipients, an m04-specific CTL line controls MCMV infection with an efficacy comparable to that of an IE1-specific CTL line. Thus, gp34 is the first noted early protein of MCMV that escapes viral immune evasion mechanisms. These data document that MCMV is held in check by a redundance of protective CD8 T cells recognizing antigenic peptides in different phases of viral gene expression.