Tat-Beclin-1: Molecular Structure
Chemical properties, amino acid sequence, and structural analysis
📌TL;DR
- •Molecular formula: C164H251N57O45
- •Molecular weight: 3028.44 Da
- •Half-life: Not formally characterized in vivo. The L-form is expected to be rapidly degraded by serum proteases. The retro-inverso D-form (Tat-D11) has enhanced resistance to proteolytic degradation and increased in vivo stability, though specific half-life values have not been published.
Amino Acid Sequence
42 amino acids
Formula
C164H251N57O45
Molecular Weight
3028.44 Da
Half-Life
Not formally characterized in vivo. The L-form is expected to be rapidly degraded by serum proteases. The retro-inverso D-form (Tat-D11) has enhanced resistance to proteolytic degradation and increased in vivo stability, though specific half-life values have not been published.
Molecular Structure#
Tat-Beclin-1 is a rationally designed chimeric peptide that combines cell-penetrating and autophagy-inducing functional domains into a single molecule.
Primary Structure#
| Property | Value |
|---|---|
| Full name | Tat-Beclin-1 (Tat-BECN1) |
| L-form sequence (Tat-L11) | YGRKKRRQRRRGGVWNATFHIWHD |
| D-form sequence (Tat-D11) | RRRQRRKKRGYGGDHWIHFTANWV (retro-inverso) |
| Total length | 24 amino acids |
| Approximate molecular weight | ~3,028 Da (L-form) |
| CAS number | 1423821-88-8 |
| Net charge at pH 7.4 | Highly positive (arginine/lysine-rich Tat domain) |
Domain Architecture#
Tat-Beclin-1 consists of three distinct functional domains:
1. HIV-1 Tat Protein Transduction Domain (11 residues)
Sequence: YGRKKRRQRRR
This domain is derived from the HIV-1 Tat protein and functions as a cell-penetrating peptide (CPP). The high density of arginine and lysine residues creates a strongly cationic sequence that enables translocation across cell membranes through interactions with negatively charged membrane phospholipids and glycosaminoglycans.
2. Diglycine Linker (2 residues)
Sequence: GG
A minimal, flexible linker connecting the cell-penetrating and autophagy-inducing domains. Glycine residues provide conformational flexibility while minimizing steric interference between the two functional domains.
3. Beclin 1 Domain (18 residues, aa 267-284)
Sequence: VWNATFHIWHD (C-terminal portion shown)
This domain is derived from a region of beclin 1 that binds to GAPR-1/GLIPR2. Beclin 1 residues 267-284 were identified through screening of beclin 1 fragments for autophagy-inducing activity. This region is also the domain through which HIV-1 Nef protein binds to and inhibits beclin 1-mediated autophagy.
L-Form vs D-Form (Retro-Inverso)#
Two forms of Tat-Beclin-1 are used in research:
| Property | L-Form (Tat-L11) | D-Form (Tat-D11) |
|---|---|---|
| Amino acid chirality | Natural L-amino acids | D-amino acids |
| Sequence direction | N-to-C (normal) | Reversed (retro-inverso) |
| Protease resistance | Low (rapidly degraded) | High (D-amino acids resist proteases) |
| In vivo stability | Low | Enhanced |
| Autophagy induction | Active | Active |
| Primary use | In vitro studies | In vivo studies |
The retro-inverso approach preserves the overall side-chain topology and functional activity while rendering the peptide backbone resistant to endogenous proteases. This is a well-established strategy for improving peptide drug stability.
Size Comparison#
| Peptide | Size | Molecular Weight | Function |
|---|---|---|---|
| Tat-Beclin-1 | 24 amino acids | ~3,028 Da | Autophagy induction |
| Humanin | 24 amino acids | ~2,687 Da | Mitochondrial-derived cytoprotection |
| GHK-Cu | 3 amino acids + Cu | ~403 Da | Wound healing, gene regulation |
| Epitalon | 4 amino acids | ~390 Da | Proposed telomerase activation |
| Vilon | 2 amino acids | ~275 Da | Proposed immune modulation |
At ~3 kDa, Tat-Beclin-1 is substantially larger than most peptide bioregulators but smaller than full proteins, placing it in a size range where cell penetration is achievable with the Tat CPP domain.
Chemical Properties#
Charge and Solubility#
The Tat domain contributes 8 positively charged residues (5 Arg + 3 Lys) at physiological pH, making Tat-Beclin-1 a highly cationic peptide. This positive charge:
- Enables membrane translocation via the Tat CPP mechanism
- Promotes water solubility
- May facilitate electrostatic interactions with negatively charged cellular components
Stability Considerations#
The L-form of Tat-Beclin-1 is susceptible to rapid proteolytic degradation by serum proteases, endopeptidases, and aminopeptidases. In practice:
- In vitro: L-form is adequate for cell culture experiments where exposure time is controlled
- In vivo: The retro-inverso D-form is preferred due to resistance to enzymatic degradation
- Storage: Lyophilized peptide should be stored at -20 degrees C. Reconstituted solutions should be aliquoted and stored frozen to minimize degradation
Target Interaction#
The beclin 1 domain of Tat-Beclin-1 interacts with GAPR-1/GLIPR2, a lipid raft-associated protein on the cytosolic face of the Golgi membrane. Structural studies have characterized the GAPR-1/beclin 1 interaction interface, confirming that Tat-Beclin-1 competes with endogenous beclin 1 for GAPR-1 binding, thereby freeing beclin 1 to activate the autophagy-initiating Class III PI3K complex.
Related Reading#
Frequently Asked Questions About Tat-Beclin-1
What type of peptide is Tat-Beclin-1?
Tat-Beclin-1 (Tat-BECN1) is a cell-permeable autophagy-inducing peptide designed by fusing 11 amino acids from the HIV-1 Tat protein transduction domain with 18 amino acids from beclin 1 (residues 267-284) via a diglycine linker. Developed by Shoji-Kawata, Levine, and colleagues at UT Southwestern, it potently induces autophagy by releasing beclin 1 from its negative regulator GAPR-1/GLIPR2 at the Golgi membrane. Preclinical studies demonstrate antiviral activity against West Nile virus, chikungunya, and HIV-1, antitumor effects in HER2-positive breast cancer xenografts, and clearance of polyglutamine protein aggregates. No human clinical trials have been conducted.
What is the half-life of Tat-Beclin-1?
The reported half-life of Tat-Beclin-1 is Not formally characterized in vivo. The L-form is expected to be rapidly degraded by serum proteases. The retro-inverso D-form (Tat-D11) has enhanced resistance to proteolytic degradation and increased in vivo stability, though specific half-life values have not been published.. Half-life can vary depending on the route of administration, formulation, and individual factors. This information is based on available preclinical or pharmacokinetic data.
What is the amino acid sequence of Tat-Beclin-1?
The amino acid sequence of Tat-Beclin-1 is YGRKKRRQRRRGGVWNATFHIWHD (L-form, Tat-L11). Tat-Beclin-1 is a chimeric peptide consisting of three domains: (1) 11 amino acids from the HIV-1 Tat protein transduction domain providing cell penetration, (2) a diglycine (GG) linker, and (3) 18 amino acids from beclin 1 (residues 267-284) providing autophagy-inducing activity through GAPR-1 binding. The L-form has an approximate molecular weight of 3,028 Da. CAS number 1423821-88-8.. This sequence determines its biological activity and binding properties.
How stable is Tat-Beclin-1 in storage?
Tat-Beclin-1 is typically supplied as a lyophilized powder for maximum stability. Tat-Beclin-1 is a chimeric peptide consisting of three domains: (1) 11 amino acids from the HIV-1 Tat protein transduction domain providing cell penetration, (2) a diglycine (GG) linker, and (3) 18 amino acids from beclin 1 (residues 267-284) providing autophagy-inducing activity through GAPR-1 binding. The L-form has an approximate molecular weight of 3,028 Da. CAS number 1423821-88-8.. When reconstituted, it should be stored refrigerated at 2-8 degrees C and protected from light. Lyophilized powder should be stored at -20 degrees C.
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