8Q7C

Cryo-EM structure of Adenovirus C5 hexon

Summary for 8Q7C

• Entry DOI: 10.2210/pdb8q7c/pdb
• EMDB information: 18212
• Descriptor: Hexon protein (1 entity in total)
• Functional Keywords: capsid protein, trimer, virus
• Biological source: Human adenovirus 5
• Total number of polymer chains: 3
• Total formula weight: 324322.85

Authors

Zoll, S.,Dhillon, A. (deposition date: 2023-08-16, release date: 2023-08-30, Last modification date: 2024-03-27)

Primary citation

Dhillon, A.,Persson, B.D.,Volkov, A.N.,Sulzen, H.,Kadek, A.,Pompach, P.,Kereiche, S.,Lepsik, M.,Danskog, K.,Uetrecht, C.,Arnberg, N.,Zoll, S.
Structural insights into the interaction between adenovirus C5 hexon and human lactoferrin.
J.Virol., 98:e0157623-e0157623, 2024

PubMed Abstract: Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackie-adenovirus receptor (CAR) for attachment and subsequently integrins for entry. CAR and integrins are however located deep within the tight junctions in the mucosa where they would not be easily accessible. Recently, a model for CAR-independent AdV entry was proposed. In this model, human lactoferrin (hLF), an innate immune protein, aids the viral uptake into epithelial cells by mediating interactions between the major capsid protein, hexon, and yet unknown host cellular receptor(s). However, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a new cryo-EM structure of HAdV-5C hexon at high resolution alongside a hybrid structure of HAdV-5C hexon complexed with human lactoferrin (hLF). These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily its N-terminal lactoferricin (Lfcin) region, interacting with hexon's hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts and also identify additional regions within hLF that critically contribute to hexon binding. Our study sheds more light on the intricate mechanism by which HAdV-C5 utilizes soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development.

PubMed: 38323814
DOI: 10.1128/jvi.01576-23

Experimental method

ELECTRON MICROSCOPY (2.9 Å)