Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 34, Pages 14079-14084Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1108777108
Keywords
crystal structure; domain-swapped dimer; protein engineering
Categories
Funding
- Gordon and Betty Moore Foundation
- National Security Science and Engineering Faculty Fellowship program
- Defense Advanced Research Projects Agency Protein Design Processes program
- Bill and Melinda Gates Foundation through Grand Challenges in Global Health Initiative [38660]
- Department of Energy
- National Institutes of Health
Ask authors/readers for more resources
Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN2) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN2 variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available