The core of the respiratory syncytial virus fusion protein is a trimeric coiled coil

被引:66
作者
Mathews, JM [1 ]
Young, TF
Tucker, SP
Mackay, JP
机构
[1] Univ Sydney, Dept Biochem, Sydney, NSW 2006, Australia
[2] Biota Holdings Ltd, Melbourne, Vic 3004, Australia
关键词
D O I
10.1128/JVI.74.13.5911-5920.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Entry into the host cell by enveloped viruses is mediated by fusion (F) or transmembrane glycoproteins. Many of these proteins share a fold comprising a trimer of antiparallel coiled-coil heterodimers, where the heterodimers are formed by two discontinuous heptad repeat motifs within the proteolytically processed chain. The F protein of human respiratory syncytial virus (RSV; the major cause of lower respiratory tract infections in infants) contains two corresponding regions that are predicted to form coiled coils (HR1 and HR2), together with a third predicted heptad repeat (HR3) located in a nonhomologous position. In order to probe the structures of these three domains and ascertain the nature of the interactions between them, we have studied the isolated HR1, HR2, and HR3 domains of RSV F by using a range of biophysical techniques, including circular dichroism, nuclear magnetic resonance spectroscopy, and sedimentation equilibrium. HR1 forms a symmetrical, trimeric coiled coil in solution (K-3 approximate to 2.2 x 10(11) M-2) Which interacts with HR2 to form a 3:3 hexamer, The HR1-BR2 interaction domains have been mapped using limited proteolysis, reversed-phase high-performance liquid chromatography, and electrospray-mass spectrometry. HR2 in isolation exists as a largely unstructured monomer, although it exhibits a tendency to form aggregates with beta-sheet-like characteristics. Only a small increase in or-helical content was observed upon the formation of the hexamer. This suggests that the RSV F glycoprotein contains a domain that closely resembles the core structure of the simian parainfluenza virus 5 fusion protein (K. A. Baker, R.E, Dutch, R. k Lamb, and T, S. Jardetzky, Mel. Cell 3:309-319, 1999). Finally, HR3 forms weak or-helical homodimers that do not appear to interact with HR1, HR2, or the HR1-HR2 complex. The results of these studies support the idea that viral fusion proteins have a common core architecture.
引用
收藏
页码:5911 / 5920
页数:10
相关论文
共 70 条
[1]   Structural basis for paramyxovirus-mediated membrane fusion [J].
Baker, KA ;
Dutch, RE ;
Lamb, RA ;
Jardetzky, TS .
MOLECULAR CELL, 1999, 3 (03) :309-319
[2]   Membrane-induced step in the activation of Sendai virus fusion protein [J].
Ben-Efraim, I ;
Kliger, Y ;
Hermesh, C ;
Shai, Y .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 285 (02) :609-625
[3]   OLIGOMERIZATION OF THE HYDROPHOBIC HEPTAD REPEAT OF GP41 [J].
BERNSTEIN, HB ;
TUCKER, SP ;
KAR, SR ;
MCPHERSON, SA ;
MCPHERSON, DT ;
DUBAY, JW ;
LEBOWITZ, J ;
COMPANS, RW ;
HUNTER, E .
JOURNAL OF VIROLOGY, 1995, 69 (05) :2745-2750
[4]   A LEUCINE ZIPPER STRUCTURE PRESENT IN THE MEASLES-VIRUS FUSION PROTEIN IS NOT REQUIRED FOR ITS TETRAMERIZATION BUT IS ESSENTIAL FOR FUSION [J].
BUCKLAND, R ;
MALVOISIN, E ;
BEAUVERGER, P ;
WILD, F .
JOURNAL OF GENERAL VIROLOGY, 1992, 73 :1703-1707
[5]   Recombinant respiratory syncytial virus from which the entire SH gene has been deleted grows efficiently in cell culture and exhibits site-specific attenuation in the respiratory tract of the mouse [J].
Bukreyev, A ;
Whitehead, SS ;
Murphy, BR ;
Collins, PL .
JOURNAL OF VIROLOGY, 1997, 71 (12) :8973-8982
[6]   STRUCTURE OF INFLUENZA HEMAGGLUTININ AT THE PH OF MEMBRANE-FUSION [J].
BULLOUGH, PA ;
HUGHSON, FM ;
SKEHEL, JJ ;
WILEY, DC .
NATURE, 1994, 371 (6492) :37-43
[7]   Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41 [J].
Caffrey, M ;
Cai, ML ;
Kaufman, J ;
Stahl, SJ ;
Wingfield, PT ;
Covell, DG ;
Gronenborn, AM ;
Clore, GM .
EMBO JOURNAL, 1998, 17 (16) :4572-4584
[8]   An efficient and cost-effective isotope labeling protocol for proteins expressed in Escherichia coli [J].
Cai, ML ;
Huang, Y ;
Sakaguchi, K ;
Clore, GM ;
Gronenborn, AM ;
Craigie, R .
JOURNAL OF BIOMOLECULAR NMR, 1998, 11 (01) :97-102
[9]   HEPTAD REPEAT SEQUENCES ARE LOCATED ADJACENT TO HYDROPHOBIC REGIONS IN SEVERAL TYPES OF VIRUS FUSION GLYCOPROTEINS [J].
CHAMBERS, P ;
PRINGLE, CR ;
EASTON, AJ .
JOURNAL OF GENERAL VIROLOGY, 1990, 71 :3075-3080
[10]   Core structure of gp41 from the HIV envelope glycoprotein [J].
Chan, DC ;
Fass, D ;
Berger, JM ;
Kim, PS .
CELL, 1997, 89 (02) :263-273