Faculty Collaboration Database

Six-helix bundle assembly and analysis of the central core of mumps virus fusion protein. Arch Biochem Biophys 2004 Jan 01;421(1):143-8

Date

12/18/2003

Pubmed ID

14678795

DOI

10.1016/j.abb.2003.09.037

Scopus ID

2-s2.0-0346848907 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

The fusion protein of enveloped viruses mediates the fusion between the viral and cellular membranes, allowing the penetration of the viral genomes into the host cell. Many of these proteins share a common fold comprising a central core trimer of anti-parallel coiled-coil heterodimers, which are formed by two discontinuous heptad repeat (HR) motifs located at the ectodomain of the fusion proteins. In this study, we constructed and purified the corresponding regions (HR1 and HR2) of mumps virus fusion protein that are predicted to form coiled coil. The HR1 and HR2 were expressed and purified separately or as a single chain connected by an amino acid linker (HR1-linker-HR2, named 2-Helix). Series of biochemical and biophysical analyses of the expressed proteins have shown that HR1 and HR2 of mumps virus fusion protein share the common features of other enveloped virus fusion proteins. CD spectral results show that HR1 forms an alpha-helical coil structure while HR2 exists as an unstructured monomer in PBS in nature. Mixtures of HR1 and HR2 could form a stable six-helix bundle, indicating the interaction of HR1 and HR2. The 2-Helix protein also shows characteristic properties of the 6-helix bundle. Therefore, mumps virus fusion protein has a common core architecture and its HR regions could be used as a drug target for virus fusion inhibitors.

Author List

Liu Y, Zhu J, Feng MG, Tien P, Gao GF

Author

Jieqing Zhu PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Chromatography, Gel
Circular Dichroism
Cross-Linking Reagents
Escherichia coli
Molecular Sequence Data
Molecular Weight
Protein Structure, Secondary
Recombinant Fusion Proteins
Repetitive Sequences, Amino Acid
Viral Fusion Proteins