PDBsum entry 2b9b

Viral protein

PDB id: 2b9b

Contents

Protein chains

478 a.a. *

Ligands

NAG ×12

Waters ×130

* Residue conservation analysis

PDB id:

2b9b

Name:

Viral protein

Title:

Structure of the parainfluenza virus 5 f protein in its metastable, pre-fusion conformation

Structure:

Fusion glycoprotein f0. Chain: a, b, c. Fragment: residues 20-477. Engineered: yes

Source:

Simian virus 5. Organism_taxid: 11207. Gene: f. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Biol. unit:

Trimer (from PQS)

Resolution:

2.85Å R-factor: 0.222 R-free: 0.259

Authors:

H.-S.Yin,X.Wen,R.G.Paterson,R.A.Lamb,T.S.Jardetzky

Key ref:

H.S.Yin et al. (2006). Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation. Nature, 439, 38-44. PubMed id: 16397490 DOI: 10.1038/nature04322

Date:

11-Oct-05 Release date: 24-Jan-06

Protein chains

P04849  (FUS_PIV5) -  Fusion glycoprotein F0 from Parainfluenza virus 5 (strain W3)

Seq: 529 a.a.

Struc: 478 a.a.*

* PDB and UniProt seqs differ at 24 residue positions (black crosses)

DOI no: 10.1038/nature04322

Nature 439:38-44 (2006)

PubMed id: 16397490

Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation.

H.S.Yin, X.Wen, R.G.Paterson, R.A.Lamb, T.S.Jardetzky.

ABSTRACT

Enveloped viruses have evolved complex glycoprotein machinery that drives the fusion of viral and cellular membranes, permitting entry of the viral genome into the cell. For the paramyxoviruses, the fusion (F) protein catalyses this membrane merger and entry step, and it has been postulated that the F protein undergoes complex refolding during this process. Here we report the crystal structure of the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a carboxy-terminal trimerization domain. The structure of the F protein shows that there are profound conformational differences between the pre- and postfusion states, involving transformations in secondary and tertiary structure. The positions and structural transitions of key parts of the fusion machinery, including the hydrophobic fusion peptide and two helical heptad repeat regions, clarify the mechanism of membrane fusion mediated by the F protein.

Selected figure(s)

Figure 2.
Figure 2: Structural changes between the pre- and postfusion F protein conformations. a, Ribbon diagram of the SV5 F-GCNt trimer. DI is yellow, DII is red, DIII is magenta, HRB is blue and GCNt is grey. b, Ribbon diagram of the hPIV3 (postfusion) trimer, similarly oriented by DI and coloured as in a. c, Ribbon diagram of a single subunit of the SV5 F-GCNt trimer, coloured as in a except for residues of HRA, which are green. d, Ribbon diagram of a single subunit of the hPIV3 F trimer, coloured as in c.

Figure 5.
Figure 5: Model of F-mediated membrane fusion. a, Structure of the prefusion conformation. HRB is blue, HRA is green, and DI, DII and DIII are yellow, red and magenta, respectively. b, 'Open stalk' conformation, in which the HRB stalk melts and separates from the prefusion head region. HRB is shown as three extended chains because the individual segments are unlikely to be helical. This conformation is consistent with a low-temperature intermediate that is inhibited by HRA peptides, but not HRB peptides. Mutations of the switch peptide residues 443, 447 and 449 would influence the formation of this intermediate by affecting stabilizing interactions between the prefusion stalk and head domains (see Fig. 4). c, A pre-hairpin intermediate can form by refolding of DIII, facilitating formation of the HRA coiled coil and insertion of the fusion peptide into the target cell membrane. This intermediate can be inhibited by peptides derived from both HRA and HRB regions. d, Before formation of the final 6HB, folding of the HRB linker onto the newly exposed DIII core, with the formation of additional -strands (see Fig. 3d, f), may stabilize the juxtaposition of viral and cellular membranes. e, The formation of the postfusion 6HB is tightly linked to membrane fusion and pore formation, juxtaposing the membrane-interacting fusion peptides and transmembrane domains.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2006, 439, 38-44) copyright 2006.

Figures were selected by the author.