2KNU

Solution structure of the transmembrane proximal region of the hepatis C virus E1 glycoprotein

Summary for 2KNU

• Entry DOI: 10.2210/pdb2knu/pdb
• NMR Information: BMRB: 16477
• Descriptor: Genome polyprotein (1 entity in total)
• Functional Keywords: hcv, pretransmembrane, glycoprotein, envelope protein, transmembrane, membrane protein
• Biological source: Hepatitis C virus
• Total number of polymer chains: 1
• Total formula weight: 3328.97

Authors

Spadaccini, R.,D'Errico, G.,D'Alessio, V.,Notomista, E.,Bianchi, A.,Merola, M.,Picone, D. (deposition date: 2009-09-04, release date: 2010-01-12, Last modification date: 2024-05-15)

Primary citation

Spadaccini, R.,D'Errico, G.,D'Alessio, V.,Notomista, E.,Bianchi, A.,Merola, M.,Picone, D.
Structural characterization of the transmembrane proximal region of the hepatitis C virus E1 glycoprotein
Biochim.Biophys.Acta, 2009

PubMed Abstract: A detailed knowledge of the mechanism of virus entry represents one of the most promising approaches to develop new therapeutic strategies. However, viral fusion is a very complex process involving fusion glycoproteins present on the viral envelope. In the two hepatitis C virus envelope proteins, E1 and E2, several membranotropic regions with a potential role in the fusion process have been identified. Among these, we have selected the 314-342 E1 region. Circular Dichroism data indicate that the peptide exhibits a clear propensity to adopt a helical folding in different membrane mimicking media, such as mixtures of water with fluorinated alcohols and phospholipids, with a slight preference for negative charged bilayers. The 3D structure of E1(314-342) peptide, calculated by 2D-NMR in a low-polarity environment, consists of two helical stretches encompassing residues 319-323 and 329-338 respectively. The peptide, presenting a largely apolar character, interacts with liposomes, as indicated by fluorescence and electron spin resonance spectra. The strength of the interaction and the deepness of peptide insertion in the phospholipid membrane are modulated by the bilayer composition, the interaction with anionic phospholipids being among the strongest ever observed. The presence of cholesterol also affects the peptide-bilayer interaction, favoring the peptide positioning close to the bilayer surface. Overall, the experimental data support the idea that this region of E1 might be involved in membrane destabilization and viral fusion; therefore it may represent a good target to develop anti-viral molecules.

PubMed: 19891955
DOI: 10.1016/j.bbamem.2009.10.018

Experimental method

SOLUTION NMR