Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin.

Abstract:

:Antigenic variation in the haemagglutinin (HA) glycoprotein of influenza virus is associated with recurrent epidemics of respiratory disease in man (for review see ref. 1). We have examined the size of structural changes necessary to alter the antigenicity of HA by determining the three-dimensional structure of the HA from an antigenic mutant containing a single amino acid substitution which was selected by growth of virus in the presence of monoclonal antibodies. Here we present evidence that the simple addition of an amino acid side chain which results in only minor local distortions of the structure of the HA is sufficient structural alteration for a virus to escape neutralization by a monoclonal antibody. Our results also demonstrate that single amino acid substitutions can cause only local changes in the HA structure, verifying the assumption made in several studies to locate antigenic sites on the HA and other molecules, and indicate that proposals of large conformational changes to account for variations in HA antigenicity are unnecessary in this case. The structure of the variant antigen has independently been successfully predicted (M. Karplus, personal communication).

journal_name

Nature

journal_title

Nature

authors

Knossow M,Daniels RS,Douglas AR,Skehel JJ,Wiley DC

doi

10.1038/311678a0

subject

Has Abstract

pub_date

1984-10-18 00:00:00

pages

678-80

issue

5987

eissn

0028-0836

issn

1476-4687

journal_volume

311

pub_type

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