Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 28 September 2007:
Vol. 317. no. 5846, pp. 1930 - 1934
DOI: 10.1126/science.1145373
Prev | Table of Contents | Next

Reports

Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4

Chih-chin Huang,1* Son N. Lam,2* Priyamvada Acharya,1 Min Tang,1 Shi-Hua Xiang,3 Syed Shahzad-ul Hussan,2 Robyn L. Stanfield,4 James Robinson,5 Joseph Sodroski,3 Ian A. Wilson,4 Richard Wyatt,1 Carole A. Bewley,2{dagger} Peter D. Kwong1{dagger}

The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 ({alpha}-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.

1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
3 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
4 Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
5 Department of Pediatrics, Tulane University Medical Center, New Orleans, LA 70112, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: caroleb{at}mail.nih.gov (C.A.B.); pdkwong{at}nih.gov (P.D.K.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION.
S. Mueller, G. Kleinau, H. Jaeschke, R. Paschke, and G. Krause (2008)
J. Biol. Chem. 283, 18048-18055
   Abstract »    Full Text »    PDF »
The HIV-1 Envelope Glycoprotein gp120 Features Four Heparan Sulfate Binding Domains, Including the Co-receptor Binding Site.
E. Crublet, J.-P. Andrieu, R. R. Vives, and H. Lortat-Jacob (2008)
J. Biol. Chem. 283, 15193-15200
   Abstract »    Full Text »    PDF »
Two Amino Acid Substitutions within the First External Loop of CCR5 Induce Human Immunodeficiency Virus-Blocking Antibodies in Mice and Chickens.
C. Pastori, A. Clivio, L. Diomede, R. Consonni, G. M. S. De Mori, R. Longhi, G. Colombo, and L. Lopalco (2008)
J. Virol. 82, 4125-4134
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)