TAT
目录号 : GC34401
TAT(YGRKKRRQRRR)是一种HIV-1病毒编码的Tat肽，可以增加异源蛋白质的产量和溶解度。
Cas No.:191936-91-1
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
TAT (YGRKKRRQRRR) is a HIV-1 virus-encoded Tat peptide, which can increase the yields and the solubility of heterologous proteins.
The Tat core domain contains the sequence 'YGRKKRRQRRR' and it has been demonstrated that Tat peptide fusions can increase the yields and solubility of heterologous proteins. The Tat peptide promotes the soluble expression of the membrane protein hLSECtin-CRD in E. coli without losing bioactivity and the protein expression level is not influenced compared with Tat-free proteins[1].
[1]. Dong G, et al. Tat peptide-mediated soluble expression of the membrane protein LSECtin-CRD in Escherichia coli. PLoS One. 2013 Dec 16;8(12):e83579.
| Cas No. | 191936-91-1 | SDF | |
| Canonical SMILES | Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2 | ||
| 分子式 | C64H119N33O13 | 分子量 | 1558.85 |
| 溶解度 | Soluble in Water | 储存条件 | Store at -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 | 0.6415 mL | 3.2075 mL | 6.415 mL |
| 5 mM | 0.1283 mL | 0.6415 mL | 1.283 mL |
| 10 mM | 0.0641 mL | 0.3207 mL | 0.6415 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。
HIV-1 TAT: An update on transcriptional and non-transcriptional functions
Biochimie 2021 Nov;190:24-35.PMID:34242726DOI:10.1016/j.biochi.2021.07.001.
Over the past decades, much have been learned about HIV-1 virus and its molecular strategies for pathogenesis. However, HIV-1 still remains an enigmatic virus, particularly because of its unique proteins. Establishment of latency and reactivation is still a puzzling question and various temporal and spatial dynamics between HIV-1 proteins itself have given us new way of thinking about its pathogenesis. HIV-1 replication depends on TAT which is a small unstructured protein and subjected to various post-translational modifications for its myriad of functions. HIV-1 TAT protein modulates the functions of various strategic cellular pathways like proteasomal machinery and inflammatory pathways to aid in HIV-1 pathogenesis. Many of the recent findings have shown that TAT is associated with exosomes, cleared from HIV-1 infected cells through its degradation by diverse routes ranging from lysosomal to proteasomal pathways. HIV-1 TAT was also found to be associated with other HIV-1 proteins including Vpr, Nef, Nucleocapsid (NC) and Rev. Interaction of TAT with Vpr and Nef increases its transactivation function, whereas, interaction of TAT with NC or Rev leads to TAT protein degradation and hence suppression of TAT functions. Research in the recent years has established that TAT is not only important for HIV-1 promoter transactivation and virus replication but also modulating multiple cellular and molecular functions leading to HIV-1 pathogenicity. In this review we discussed various transcriptional and non-transcriptional HIV-1 TAT functions which modulate host cell metabolism during HIV-1 pathogenesis.
Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure
Viruses 2020 Apr 8;12(4):415.PMID:32276443DOI:10.3390/v12040415.
The human immunodeficiency virus type 1 (HIV) establishes a chronic infection that can be well controlled, but not cured, by combined antiretroviral therapy (cART). Interventions have been explored to accomplish a functional cure, meaning that a patient remains infected but HIV is undetectable in the blood, with the aim of allowing patients to live without cART. TAT, the viral transactivator of transcription protein, plays a critical role in controlling HIV transcription, latency, and viral rebound following the interruption of cART treatment. Therefore, a logical approach for controlling HIV would be to block TAT. Tackling TAT with inhibitors has been a difficult task, but some recent discoveries hold promise. Two anti-HIV proteins, Nullbasic (a mutant of TAT) and HT1 (a fusion of HEXIM1 and TAT functional domains) inhibit viral transcription by interfering with the interaction of TAT and cellular factors. Two small molecules, didehydro-cortistatin A (dCA) and triptolide, inhibit TAT by different mechanisms: dCA through direct binding and triptolide through enhanced proteasomal degradation. Finally, two Tat-based vaccines under development elicit Tat-neutralizing antibodies. These vaccines have increased the levels of CD4+ cells and reduced viral loads in HIV-infected people, suggesting that the new vaccines are therapeutic. This review summarizes recent developments of anti-Tat agents and how they could contribute to a functional cure for HIV.
Genetic variation and function of the HIV-1 TAT protein
Med Microbiol Immunol 2019 Apr;208(2):131-169.PMID:30834965DOI:10.1007/s00430-019-00583-z.
Human immunodeficiency virus type 1 (HIV-1) encodes a transactivator of transcription (TAT) protein, which has several functions that promote viral replication, pathogenesis, and disease. Amino acid variation within TAT has been observed to alter the functional properties of TAT and, depending on the HIV-1 subtype, may produce TAT phenotypes differing from viruses' representative of each subtype and commonly used in in vivo and in vitro experimentation. The molecular properties of TAT allow for distinctive functional activities to be determined such as the subcellular localization and other intracellular and extracellular functional aspects of this important viral protein influenced by variation within the TAT sequence. Once TAT has been transported into the nucleus and becomes engaged in transactivation of the long terminal repeat (LTR), various TAT variants may differ in their capacity to activate viral transcription. Post-translational modification patterns based on these amino acid variations may alter interactions between TAT and host factors, which may positively or negatively affect this process. In addition, the ability of HIV-1 to utilize or not utilize the transactivation response (TAR) element within the LTR, based on genetic variation and cellular phenotype, adds a layer of complexity to the processes that govern Tat-mediated proviral DNA-driven transcription and replication. In contrast, cytoplasmic or extracellular localization of TAT may cause pathogenic effects in the form of altered cell activation, apoptosis, or neurotoxicity. TAT variants have been shown to differentially induce these processes, which may have implications for long-term HIV-1-infected patient care in the antiretroviral therapy era. Future studies concerning genetic variation of TAT with respect to function should focus on variants derived from HIV-1-infected individuals to efficiently guide Tat-targeted therapies and elucidate mechanisms of pathogenesis within the global patient population.
HIV-1 TAT amino acid residues that influence Tat-TAR binding affinity: a scoping review
BMC Infect Dis 2023 Mar 17;23(1):164.PMID:36932337DOI:10.1186/s12879-023-08123-0.
HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (TAT) protein due to its key function in viral transcription. The TAT protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific TAT protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the TAT protein and/or individual TAT amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data to determine (1) the regions of the TAT protein that may be involved in TAR binding, (2) key TAT amino acids involved in TAR binding and (3) if TAT subtype-specific variation influences TAR binding. A total of thirteen studies met our inclusion criteria and the key findings were that (1) both N-terminal and C-terminal amino acids outside the basic domain (47-59) may be important in increasing Tat-TAR binding affinity, (2) substitution of the amino acids Lysine and Arginine (47-59) resulted in a reduction in binding affinity to TAR, and (3) none of the included studies have investigated TAT subtype-specific substitutions and therefore no commentary could be made regarding which subtype may have a higher Tat-TAR binding affinity. Future studies investigating Tat-TAR binding should therefore use full-length TAT proteins and compare subtype-specific variations. Studies of such a nature may help explain why we see differential pathogenesis and prevalence when comparing HIV-1 subtypes.
The ins and outs of HIV-1 TAT
Traffic 2012 Mar;13(3):355-63.PMID:21951552DOI:10.1111/j.1600-0854.2011.01286.x.
HIV-1 encodes for the small basic protein TAT (86-101 residues) that drastically enhances the efficiency of viral transcription. The mechanism enabling TAT nuclear import is not yet clear, but studies using reporter proteins fused to the TAT basic domain indicate that TAT could reach the nucleus by passive diffusion. TAT also uses an unusual transcellular transport pathway. The first step of this pathway involves high-affinity binding of TAT to phosphatidylinositol (4,5) bisphosphate (PI(4,5)P(2)), a phospholipid that is concentrated in the inner leaflet of the plasma membrane and enables TAT recruitment at this level. TAT then crosses the plasma membrane to reach the outside medium. Although unconventional, TAT secretion by infected cells is highly active, and export is the major destination for HIV-1 TAT. Secreted TAT can bind to a variety of cell types using several different receptors. Most of them will allow TAT endocytosis. Upon internalization, low endosomal pH triggers a conformational change in TAT that results in membrane insertion. Later steps of TAT translocation to the target-cell cytosol are assisted by Hsp90, a general cytosolic chaperone. Cytosolic TAT can trigger various cell responses. Indeed, accumulating evidence suggests that extracellular TAT acts as a viral toxin that affects the biological activity of different cell types and has a key role in acquired immune-deficiency syndrome development. This review focuses on some of the recently identified molecular details underlying the unusual transcellular transport pathway used by TAT, such as the role of the single Trp in TAT for its membrane insertion and translocation.