What does it take to bind CAR?
Lane K Law1, Beverly L Davidson
1Program in Gene Therapy, Genetics Ph.D. Program, University of Iowa, Iowa City, 52242, USA.
Abstract:
Recombinant adenoviruses (Ads) have been used as reagents for biological studies and therapeutic protocols for the treatment of human patients. The two most commonly used Ads, Ad2 and Ad5, infect a broad range of tissues through interaction with the coxsackie and adenovirus receptor CAR. Both mutational analyses and crystal structure data have established residues in the fiber knob and shaft critical for Ad-CAR binding. In this report we review the contributions of various residues to Ad-CAR binding, taking into consideration the documented cellular tropism of other Ad serotypes.
Insights
Recombinant adenoviruses (Ads) are vital for research and therapy. This review details key residues in Ad2 and Ad5 fibers essential for binding the coxsackie and adenovirus receptor (CAR), influencing tissue tropism.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Recombinant adenoviruses (Ads) are widely employed as biological reagents and in therapeutic strategies for human diseases.
- Adenovirus serotypes Ad2 and Ad5 are common, utilizing the coxsackie and adenovirus receptor (CAR) for broad tissue tropism.
Purpose of the Study:
- To review the critical residues in adenovirus fiber proteins responsible for CAR binding.
- To correlate Ad-CAR binding interactions with the known cellular tropism of various adenovirus serotypes.
Main Methods:
- Analysis of existing mutational data on adenovirus fiber proteins.
- Review of crystal structure data elucidating Ad-CAR interactions.
- Integration of findings with established adenovirus serotype cellular tropism.
Main Results:
- Specific residues within the fiber knob and shaft domains are definitively identified as crucial for Ad-CAR binding.
- Understanding these residues provides insights into the molecular basis of adenovirus tissue tropism.
Conclusions:
- The interaction between adenovirus fiber proteins and CAR is mediated by specific residues in the fiber knob and shaft.
- This knowledge is fundamental for engineering adenovirus tropism for therapeutic and research applications.
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