Skip NavigationSkip to Content
Return Return to Search Results

Monomerization of Viral Entry Inhibitor Griffithsin Elucidates the Relationship between Multivalent Binding to Carbohydrates and anti-HIV Activity

  1. Author:
    Moulaei, T.
    Shenoy, S. R.
    Giomarelli, B.
    Thomas, C.
    McMahon, J. B.
    Dauter, Z.
    O'Keefe, B. R.
    Wlodawer, A.

  2. Author Address

    [Shenoy, Shilpa R.; Giomarelli, Barbara; Thomas, Cheryl; McMahon, James B.; O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Moulaei, Tinoush; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Shenoy, Shilpa R.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. [Dauter, Zbigniew] Argonne Natl Lab, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Natl Canc Inst, Argonne, IL 60439 USA.;O'Keefe, BR, NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.;okeefeba@mail.nih.gov wlodawer@nih.gov
    1. Year: 2010
    2. Date: Sep
  2. Journal: Structure
    1. 18
    2. 9
    3. Pages: 1104-1115
  4. Type of Article: Article
  5. ISSN: 0969-2126
  1. Abstract:

    Mutations were introduced to the domain-swapped homodimer of the antiviral lectin griffithsin (GRFT). Whereas several single and double mutants remained dimeric, insertion of either two or four amino acids at the dimerization interface resulted in a monomeric form of the protein (mGRFT). Monomeric character of the modified proteins was confirmed by sedimentation equilibrium ultracentrifugation and by their high resolution X-ray crystal structures, whereas their binding to carbohydrates was assessed by isothermal titration calorimetry. Cell-based antiviral activity assays utilizing different variants of mGRFT indicated that the monomeric form of the lectin had greatly reduced activity against HIV-1, suggesting that the antiviral activity of GRFT stems from crosslinking and aggregation of viral particles via multivalent interactions between GRFT and oligosaccharides present on HIV envelope glycoproteins. Atomic resolution crystal structure of a complex between mGRFT and nonamannoside revealed that a single mGRFT molecule binds to two different nonamannoside molecules through all three carbohydrate-binding sites present on the monomer.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.str.2010.05.016
  3. View record in Web of Science®
  4. WOS: 000281836400007

Library Notes

  1. Fiscal Year: FY2009-2010
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel