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DNA binding provides a molecular strap activating the adenovirus proteinase
Sayan Gupta1, Walter F Mangel, William J McGrath
1Center for Synchrotron Biosciences, Department of Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Molecular & Cellular Proteomics : MCP
|June 29, 2004
Summary
Human adenovirus proteinase (AVP) activity is enhanced by pVIc peptide and viral DNA. Cofactor binding induces conformational changes, revealing a model for AVP activation by DNA and pVIc.
Area of Science:
- Biochemistry
- Structural Biology
- Virology
Background:
- Human adenovirus proteinase (AVP) is essential for viral replication.
- AVP activity is known to be modulated by cofactors, including a peptide (pVIc) and viral DNA.
Purpose of the Study:
- To map cofactor binding sites on AVP using synchrotron protein footprinting.
- To elucidate the conformational changes in AVP upon binding of pVIc and/or DNA.
- To develop a structural model for DNA binding and AVP activation.
Main Methods:
- Synchrotron protein footprinting to identify solvent-accessible residues.
- Analysis of hydroxyl radical protection patterns.
- Construction of a three-dimensional model of DNA-AVP interaction.
Main Results:
- pVIc binding, alone or with DNA, induced significant conformational changes near the AVP active site.
- DNA binding protected specific residues on both AVP subdomains.
- A model showed DNA binding alters domain orientation, partially activating AVP.
Conclusions:
- Both pVIc and viral DNA contribute to the full activation of human adenovirus proteinase.
- Cofactor binding induces distinct and cooperative conformational changes in AVP.
- Understanding AVP activation provides insights into adenovirus replication mechanisms.