PXD045900

PXD045900 is an original dataset announced via ProteomeXchange.

Title	Structural Insights into the Interaction Between Adenovirus 5C Hexon and Human Lactoferrin
Description	Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human infective species C AdVs, such as HAdV-C5, utilise 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, Lactoferrin (LF), 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). Yet, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a novel cryo-EM structure of HAd-5C hexon at high resolution alongside a hybrid structure of human lactoferrin (hLF) complexed with HAdV-5C hexon. These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily via its N-terminal Lactoferricin (Lfcin) region, interacting with hexon's hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts but 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 utilises soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development.
HostingRepository	PRIDE
AnnounceDate	2024-02-03
AnnouncementXML	Submission_2024-02-02_23:58:07.719.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petr Pompach
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-04 08:00:57	ID requested
⏵ 1	2024-02-02 23:58:08	announced

10.1128/JVI.01576-23;

submitter keyword: immune-evasion, cryo-EM,Adenovirus, lactoferrin, viral-entry

Sebastian Zoll
contact affiliation	Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 542/2, 16000, Prague, Czech Republic
contact email	sebastian.zoll@uochb.cas.cz
lab head
Petr Pompach
contact affiliation	Intitute of Biotechnology
contact email	petr.pompach@ibt.cas.cz
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD045900

PRIDE project URI

• PRIDE
  1. PXD045900
     1. Label: PRIDE project
     2. Name: Structural Insights into the Interaction Between Adenovirus 5C Hexon and Human Lactoferrin