[English] 日本語
![](img/lk-miru.gif)
- PDB-6nxe: Cryo-EM Reconstruction of Protease-Activateable Adeno-Associated ... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6nxe | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM Reconstruction of Protease-Activateable Adeno-Associated Virus 9 (AAV9-L001) | ||||||
![]() | Capsid protein VP1 | ||||||
![]() | VIRUS / AAV / activatable / gene therapy / provector | ||||||
Function / homology | Phospholipase A2-like domain / Phospholipase A2-like domain / Parvovirus coat protein VP2 / Parvovirus coat protein VP1/VP2 / Parvovirus coat protein VP2 / Capsid/spike protein, ssDNA virus / T=1 icosahedral viral capsid / structural molecule activity / Capsid protein VP1![]() | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.16 Å | ||||||
![]() | Bennett, A.B. / Agbandje-Mckenna, M. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Protease-Activatable Adeno-Associated Virus Vector for Gene Delivery to Damaged Heart Tissue. Authors: Caitlin M Guenther / Mitchell J Brun / Antonette D Bennett / Michelle L Ho / Weitong Chen / Banghe Zhu / Michael Lam / Momona Yamagami / Sunkuk Kwon / Nilakshee Bhattacharya / Duncan Sousa / ...Authors: Caitlin M Guenther / Mitchell J Brun / Antonette D Bennett / Michelle L Ho / Weitong Chen / Banghe Zhu / Michael Lam / Momona Yamagami / Sunkuk Kwon / Nilakshee Bhattacharya / Duncan Sousa / Annicka C Evans / Julie Voss / Eva M Sevick-Muraca / Mavis Agbandje-McKenna / Junghae Suh / ![]() Abstract: Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, and low immunogenicity compared to other viruses. However, ...Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, and low immunogenicity compared to other viruses. However, its adoption as a safe and effective delivery vector for certain diseases relies on altering its tropism to deliver transgenes to desired cell populations. To this end, we have developed a protease-activatable AAV vector, named provector, that responds to elevated extracellular protease activity commonly found in diseased tissue microenvironments. The AAV9-based provector is initially inactive, but then it can be switched on by matrix metalloproteinases (MMP)-2 and -9. Cryo-electron microscopy and image reconstruction reveal that the provector capsid is structurally similar to that of AAV9, with a flexible peptide insertion at the top of the 3-fold protrusions. In an in vivo model of myocardial infarction (MI), the provector is able to deliver transgenes site specifically to high-MMP-activity regions of the damaged heart, with concomitant decreased delivery to many off-target organs, including the liver. The AAV provector may be useful in the future for enhanced delivery of transgenes to sites of cardiac damage. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 5.2 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 0535MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 60939.168 Da / Num. of mol.: 60 / Fragment: UNP residues 219-736 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Adeno-associated virus / Type: VIRUS / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() |
Details of virus | Empty: NO / Enveloped: NO / Isolate: SEROTYPE / Type: VIRION |
Virus shell | Diameter: 260 nm / Triangulation number (T number): 1 |
Buffer solution | pH: 7.4 |
Buffer component | Name: TD Buffer / Formula: PBS-MK |
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: The sample was monodisperse. |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: DIRECT ELECTRON DE-20 (5k x 3k) |
-
Processing
EM software |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
3D reconstruction | Resolution: 3.16 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 114044 / Symmetry type: POINT | ||||||||||||
Atomic model building | Space: REAL | ||||||||||||
Atomic model building | PDB-ID: 3UX1 Pdb chain-ID: A / Accession code: 3UX1 / Source name: PDB / Type: experimental model |