Probing the sialic acid binding site of the hemagglutinin-neuraminidase of Newcastle disease virus: Identification of key amino acids involved in cell binding, catalysis, and fusion

Helen Connaris, Toru Takimoto, Rupert Russell, Susan Crennell, Ibrahim Moustafa, Allen Portner, Garry Taylor

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

We recently reported the first crystal structure of a paramyxovirus hemagglutinin-neuraminidase (HN) from Newcastle disease virus. This multifunctional protein is responsible for binding to cellular sialyl-glycoconjugate receptors, promotion of fusion through interaction with the second viral surface fusion (F) glycoprotein, and processing progeny virions by removal of sialic acid from newly synthesized viral coat proteins. Our structural studies suggest that HN possesses a single sialic acid recognition site that can be switched between being a binding site and a catalytic site. Here we examine the effect of mutation of several conserved amino acids around the binding site on the hemagglutination, neuraminidase, and fusion functions of HN. Most mutations around the binding site result in loss of neuraminidase activity, whereas the effect on receptor binding is more variable. Residues E401, R416, and Y526 appear to be key for receptor binding. The increase in fusion promotion seen in some mutants that lack receptor binding activity presents a conundrum. We propose that in these cases HN may be switched into a fusion-promoting state through a series of conformational changes that propagate from the sialic acid binding site through to the HN dimer interface. These results further support the single-site model and suggest certain residues to be important for the triggering of fusion.

Original languageEnglish (US)
Pages (from-to)1816-1824
Number of pages9
JournalJournal of virology
Volume76
Issue number4
DOIs
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Probing the sialic acid binding site of the hemagglutinin-neuraminidase of Newcastle disease virus: Identification of key amino acids involved in cell binding, catalysis, and fusion'. Together they form a unique fingerprint.

Cite this