[English] 日本語
![](img/lk-miru.gif)
- PDB-6avu: Human alpha-V beta-3 Integrin (open conformation) in complex with... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6avu | ||||||
---|---|---|---|---|---|---|---|
Title | Human alpha-V beta-3 Integrin (open conformation) in complex with the therapeutic antibody LM609 | ||||||
![]() |
| ||||||
![]() | ![]() ![]() | ||||||
Function / homology | ![]() integrin alphav-beta6 complex / integrin alphav-beta8 complex / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / : / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Borst, A.J. / James, Z.N. / Zagotta, W.N. / Ginsberg, M. / Rey, F.A. / DiMaio, F. / Backovic, M. / Veesler, D. | ||||||
![]() | ![]() Title: The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human αβ Integrin via Steric Hindrance. Authors: Andrew J Borst / Zachary M James / William N Zagotta / Mark Ginsberg / Felix A Rey / Frank DiMaio / Marija Backovic / David Veesler / ![]() ![]() Abstract: The LM609 antibody specifically recognizes αβ integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II ...The LM609 antibody specifically recognizes αβ integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αβ-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αβ integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αβ. Using single-particle electron microscopy, we show that LM609 binds at the interface between the β-propeller domain of the α chain and the βI domain of the β chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 280.5 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 189.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 7013MC ![]() 7011C ![]() 7012C ![]() 5opyC ![]() 6avqC ![]() 6avrC C: citing same article ( M: map data used to model this data |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | ![]() Mass: 105894.188 Da / Num. of mol.: 1 / Fragment: UNP residues 31-987 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
---|---|
#2: Protein | ![]() Mass: 76523.125 Da / Num. of mol.: 1 / Fragment: UNP residues 27-718 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
#3: Antibody | Mass: 27223.100 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
#4: Antibody | Mass: 23628.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: Quaternary complex of human alpha-V beta-3 integrin with the Fab LM609 Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.23 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
EM staining | Type: NEGATIVE / Material: Uranyl formate |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat 2/0.5 |
-
Electron microscopy imaging
Microscopy | Model: FEI TECNAI 12 |
---|---|
Electron gun | Electron source![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN ULTRASCAN 4000 (4k x 4k) |
-
Processing
EM software |
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|
CTF correction![]() | Type: NONE | |||||||||
3D reconstruction![]() | Resolution: 35 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 650 / Symmetry type: POINT | |||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |