Competition for membrane receptors: Norovirus detachment via lectin attachment
Artikel i vetenskaplig tidskrift, 2019

Virus internalization into the host cells occurs via multivalent interactions, in which a single virus binds to multiple receptors in parallel. Because of analytical and experimental limitations this complex type of interaction is still poorly understood and quantified. Herein, the multivalent interaction of norovirus-like particles (noroVLPs) with H or B type 1 glycosphingolipids (GSLs), embedded in a supported phospholipid bilayer, is investigated by following the competition between noroVLPs and a lectin (from Ralstonia solanacearum) upon binding to these GSLs. Changes in noroVLP and lectin coverage, caused by competition, were monitored for both GSLs and at different GSL concentrations using quartz crystal microbalance with dissipation monitoring. The study yields information about the minimum GSL concentration needed for (i) noroVLPs to achieve firm attachment to the bilayer prior to competition and to (ii) remain firmly attached to the bilayer during competition. We show that these two concentrations are almost identical for the H type 1-noroVLP interaction but differ for B type 1, indicating an accumulation of B type 1 GSLs in the noroVLP-bilayer interaction area. Furthermore, the GSL concentration required for firm attachment is significantly larger for H type 1 than for B type 1, indicating a higher affinity of noroVLP toward B type 1. This finding is supported by extracting the energy of single noroVLP-H type 1 and noroVLP-B type 1 bonds from the competition kinetics, which were estimated to be 5 and 6 kcal/mol, respectively. This demonstrates the potential of utilizing competitive binding kinetics to analyze multivalent interactions, which has remained difficult to quantify using conventional approaches.

Författare

Nagma Parveen

KU Leuven

Chalmers, Fysik, Biologisk fysik

Gustaf E Rydell

Göteborgs universitet

G. Larson

Göteborgs universitet

V. P. Hytonen

Tampereen Yliopisto

Vladimir Zhdanov

Russian Academy of Sciences

Chalmers, Fysik, Biologisk fysik

Fredrik Höök

Chalmers, Fysik, Biologisk fysik

Stephan Block

Chalmers, Fysik, Biologisk fysik

Freie Universität Berlin

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 141 41 16303-16311

Ämneskategorier

Biokemi och molekylärbiologi

Annan medicinsk grundvetenskap

Biofysik

DOI

10.1021/jacs.9b0603h

PubMed

31533424

Mer information

Senast uppdaterat

2019-11-25