4ZDG

Structure of the Adenovirus 14p1 knob domain

Summary for 4ZDG

• Entry DOI: 10.2210/pdb4zdg/pdb
• Descriptor: Fiber protein (1 entity in total)
• Functional Keywords: adenovirus 14, strain p1, fibre knob, head domain, viral protein
• Biological source: Human adenovirus 14p1
• Total number of polymer chains: 3
• Total formula weight: 71731.51

Authors

Fender, P.,Ducournau, C.,Zubieta, C. (deposition date: 2015-04-17, release date: 2015-09-09, Last modification date: 2024-01-10)

Primary citation

Wang, H.,Ducournau, C.,Saydaminova, K.,Richter, M.,Yumul, R.,Ho, M.,Carter, D.,Zubieta, C.,Fender, P.,Lieber, A.
Intracellular Signaling and Desmoglein 2 Shedding Triggered by Human Adenoviruses Ad3, Ad14, and Ad14P1.
J.Virol., 89:10841-10859, 2015

PubMed Abstract: We recently discovered that desmoglein 2 (DSG2) is a receptor for human adenovirus species B serotypes Ad3, Ad7, Ad11, and Ad14. Ad3 is considered to be a widely distributed human pathogen. Ad3 binding to DSG2 triggers the transient opening of epithelial junctions. Here, we further delineate the mechanism that leads to DSG2-mediated epithelial junction opening in cells exposed to Ad3 and recombinant Ad3 fiber proteins. We identified an Ad3 fiber knob-dependent pathway that involves the phosphorylation of mitogen-activated protein (MAP) kinases triggering the activation of the matrix-metalloproteinase ADAM17. ADAM17, in turn, cleaves the extracellular domain of DSG2 that links epithelial cells together. The shed DSG2 domain can be detected in cell culture supernatant and also in serum of mice with established human xenograft tumors. We then extended our studies to Ad14 and Ad14P1. Ad14 is an important research and clinical object because of the recent appearance of a new, more pathogenic strain (Ad14P1). In a human epithelial cancer xenograft model, Ad14P1 showed more efficient viral spread and oncolysis than Ad14. Here, we tested the hypothesis that a mutation in the Ad14P1 fiber knob could account for the differences between the two strains. While our X-ray crystallography studies suggested an altered three-dimensional (3D) structure of the Ad14P1 fiber knob in the F-G loop region, this did not significantly change the fiber knob affinity to DSG2 or the intracellular signaling and DSG2 shedding in epithelial cancer cells.

PubMed: 26292319
DOI: 10.1128/JVI.01425-15

Experimental method

X-RAY DIFFRACTION (3.2 Å)