9CLI

Cryo-EM model derived from localized reconstruction of human adenovirus (Ad5)-hexon-FX complex at 3.6A resolution

Summary for 9CLI

• Entry DOI: 10.2210/pdb9cli/pdb
• EMDB information: 45675
• Descriptor: Hexon protein, Coagulation factor X, CALCIUM ION (3 entities in total)
• Functional Keywords: adenovirus, hexon, coagulation factor x, coagulation factor ii, prothrombin, complex, interactions, virus
• Biological source: Human adenovirus 5; More
• Total number of polymer chains: 4
• Total formula weight: 379890.14

Authors

Reddy, V.S.,Ma, O.X. (deposition date: 2024-07-11, release date: 2024-11-27)

Primary citation

Mudrick, H.E.,Lu, S.C.,Bhandari, J.,Barry, M.E.,Hemsath, J.R.,Andres, F.G.M.,Ma, O.X.,Barry, M.A.,Reddy, V.S.
Structure-derived insights from blood factors binding to the surfaces of different adenoviruses.
Nat Commun, 15:9768-9768, 2024

PubMed Abstract: 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.

PubMed: 39528527
DOI: 10.1038/s41467-024-54049-9

Experimental method

ELECTRON MICROSCOPY (3.61 Å)