2W9L

CANINE ADENOVIRUS TYPE 2 FIBRE HEAD IN COMPLEX WITH CAR DOMAIN D1 AND SIALIC ACID

Summary for 2W9L

• Entry DOI: 10.2210/pdb2w9l/pdb
• Related: 1EAJ 1F5W 1JEW 1KAC 1P69 1P6A 1RSF 2J12 2J1K 2J2J
• Descriptor: COXSACKIEVIRUS AND ADENOVIRUS RECEPTOR, FIBRE PROTEIN, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose, ... (5 entities in total)
• Functional Keywords: immunoglobulin domain, car, knob, fiber, fibre, cav-2, canine, complex, erythrocyte, sialic acid, glycoprotein, fiber head, adenovirus, fibre head, lipoprotein, fiber protein, cell junction, cell adhesion, red blood cell, coxsackievirus, phosphoprotein, membrane, secreted, receptor, palmitate, domain d1, host-virus interaction, virus-receptor complex, transmembrane, cell membrane, sialyl-lactose, tight junction, phosphorylation, hemagglutination
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 24
• Total formula weight: 431539.88

Authors

Seiradake, E.,Henaff, D.,Wodrich, H.,Billet, O.,Perreau, M.,Hippert, C.,Mennechet, F.,Schoehn, G.,Lortat-Jacob, H.,Dreja, H.,Ibanes, S.,Kalatzis, V.,Wang, J.P.,Finberg, R.W.,Cusack, S.,Kremer, E.J. (deposition date: 2009-01-26, release date: 2009-03-17, Last modification date: 2023-12-13)

Primary citation

Seiradake, E.,Henaff, D.,Wodrich, H.,Billet, O.,Perreau, M.,Hippert, C.,Mennechet, F.,Schoehn, G.,Lortat-Jacob, H.,Dreja, H.,Ibanes, S.,Kalatzis, V.,Wang, J.P.,Finberg, R.W.,Cusack, S.,Kremer, E.J.
The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.
PLoS Pathog., 5:e1000277-e1000277, 2009

PubMed Abstract: Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad-erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models.

PubMed: 19119424
DOI: 10.1371/journal.ppat.1000277

Experimental method

X-RAY DIFFRACTION (2.91 Å)