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Common molecular scaffold for two unrelated RGD molecules
K R Ely1, T J Kunicki, R Kodandapani
1Structural Biology Program, La Jolla Cancer Research Foundation, CA 92037, USA.
Protein Engineering
|August 1, 1995
Summary
The arginine-glycine-aspartic acid (RGD) sequence is key for cell adhesion. Structural analysis reveals a common molecular scaffold presenting the RGD site for receptor recognition in unrelated proteins.
Area of Science:
- Structural biology
- Molecular recognition
- Cell adhesion
Background:
- The arginine-glycine-aspartic acid (RGD) sequence mediates cell adhesion by binding to integrin receptors.
- This tripeptide is found in various proteins like fibronectin and fibrinogen.
- The precise conformational orientation of the RGD sequence is crucial for specific receptor binding.
Purpose of the Study:
- To investigate the structural basis of RGD sequence recognition by cell surface receptors.
- To compare the structures of fibronectin (FNIII10) and an RGD-mimicking antibody fragment (OPG2) containing the RGD/RYD sequence.
Main Methods:
- X-ray crystallography was used to determine the 3D structures of FNIII10 and OPG2.
- Comparative structural analysis was performed on the determined structures.
Main Results:
- Both FNIII10 and OPG2 adopt a beta-barrel fold with antiparallel beta-sheets surrounding a hydrophobic core.
- A common molecular scaffold was identified in both unrelated molecules.
- The RGD/RYD sequences are positioned in structurally analogous loops within this scaffold, facilitating stereochemical presentation for receptor interaction.
Conclusions:
- A conserved molecular scaffold underlies the presentation of the RGD sequence for integrin recognition.
- This structural similarity in unrelated proteins highlights a conserved mechanism for mediating cell adhesion.