Structure-derived insights from blood factors binding to the surfaces of different adenoviruses.

Autor: Mudrick HE; Molecular Pharmacology and Experimental Therapeutics Graduate Program, Mayo Clinic, Rochester, MN, 55905, USA., Lu SC; Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, 55905, USA., Bhandari J; The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA., Barry ME; Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, 55905, USA., Hemsath JR; Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, 55905, USA., Andres FGM; Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, 55905, USA.; Department of Immunology, Department of Molecular Medicine, Mayo Clinic, Rochester, MN, 55905, USA., Ma OX; The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA., Barry MA; Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, 55905, USA. mab@mayo.edu.; Department of Immunology, Department of Molecular Medicine, Mayo Clinic, Rochester, MN, 55905, USA. mab@mayo.edu., Reddy VS; The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA. vsreddy@umn.edu.; Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, 92037, USA. vsreddy@umn.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 11; Vol. 15 (1), pp. 9768. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1038/s41467-024-54049-9
Abstrakt: The tropism of adenoviruses (Ads) is significantly influenced by the binding of various blood factors. To investigate differences in their binding, we conducted cryo-EM analysis on complexes of several human adenoviruses with human platelet factor-4 (PF4), coagulation factors FII (Prothrombin), and FX. While we observed EM densities for FII and FX bound to all the species-C adenoviruses examined, no densities were seen for PF4, even though PF4 can co-pellet with various Ads. Similar to FX, the γ-carboxyglutamic acid (Gla) domain of FII binds within the surface cavity of hexon trimers. While FII binds equally to species-C Ads: Ad5, Ad6, and Ad657, FX exhibits significantly better binding to Ad5 and Ad657 compared to Ad6. Although only the FX-Gla domain is observed at high-resolution (3.7 Å), the entire FX is visible at low-resolution bound to Ad5 in three equivalent binding modes consistent with the 3-fold symmetric hexon. Only the Gla and kringle-1 domains of FII are visible on all the species-C adenoviruses, where the rigid FII binds in an upright fashion, in contrast to the flexible and bent FX. These data suggest that differential binding of FII and FX may shield certain species-C adenoviruses differently against immune molecules, thereby modulating their tropism.
Competing Interests: Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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