Database accession: MF6240001
Name: Human respiratory syncytial virus fusion protein core
PDB ID: 1g2c
Experimental method: X-ray (2.30 Å)
Assembly: heterohexamer
Source organism: Human respiratory syncytial virus A
Primer publication of the structure:
Zhao X, Singh M, Malashkevich VN, Kim PS
Structural characterization of the human respiratory syncytial virus fusion protein core.
(2000) Proc. Natl. Acad. Sci. U.S.A. 97: 14172-7
PMID: 11106388
Abstract:
Human respiratory syncytial virus (HRSV) is a major cause of a number of severe respiratory diseases, including bronchiolitis and pneumonia, in infants and young children. The HRSV F protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two heptad-repeat regions within the HRSV F sequence were predicted by the computer program learncoil-vmf. These regions are thought to form trimer-of-hairpins-like structures, similar to those found in the fusion proteins of several enveloped viruses. The hairpin structure likely brings the viral and cellular membranes into close apposition, thereby facilitating membrane fusion and subsequent viral entry. Here, we show that peptides, denoted HR-N and HR-C, corresponding to the heptad-repeat regions from the N-terminal and C-terminal segments of the HRSV F protein, respectively, form a stable alpha-helical trimer of heterodimers. The HRSV N/C complex was crystallized and its x-ray structure was determined at 2.3-A resolution. As anticipated, the complex is a six-helix bundle in which the HR-N peptides form a three-stranded, central coiled coil, and the HR-C peptides pack in an antiparallel manner into hydrophobic grooves on the coiled-coil surface. There is remarkable structural similarity between the HRSV N/C complex and the fusion protein core of other viruses, including HIV-1 gp41. In addition, earlier work has shown that HRSV HR-C peptides, like the HIV-1 gp41 C peptides, inhibit viral infection. Thus, drug discovery and vaccine development strategies aimed at inhibiting viral entry by blocking hairpin formation may be applied to the inhibition of HRSV.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
Biological process:
positive regulation of syncytium formation by virus The process in which a virus increases the frequency, rate or extent of the formation of a syncytium, a mass of cytoplasm containing several nuclei enclosed within a single plasma membrane, by the fusion of the plasma membranes of two or more individual cells.
fusion of virus membrane with host plasma membrane Fusion of a viral membrane with the host cell membrane during viral entry. Results in release of the virion contents into the cytoplasm.
Cellular component:
viral envelope The lipid bilayer of a virion that surrounds the protein capsid. May also contain glycoproteins.
host cell plasma membrane The plasma membrane surrounding a host cell.
integral component of membrane The component of a membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
virion membrane The lipid bilayer surrounding a virion.
Structural annotations of the participating protein chains.Entry contents: 6 distinct polypeptide molecules
Chains: A, B, C, D, E, F
Notes: Chains G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W and X were removed as chains A, B, C, D, E and F represent the biologically relevant dimer.
Number of unique protein segments: 2
Name: Fusion glycoprotein F0
Source organism: Human respiratory syncytial virus A
Length: 52 residues
Sequence:Sequence according to PDB SEQRESLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNK
UniProtKB AC: P11209 (positions: 158-209) Coverage: 9.1%
UniRef90 AC: UniRef90_P03420 (positions: 158-209)
Name: Fusion glycoprotein F0
Source organism: Human respiratory syncytial virus A
Length: 43 residues
Sequence:Sequence according to PDB SEQRESFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG
UniProtKB AC: P11209 (positions: 477-519) Coverage: 7.5%
UniRef90 AC: UniRef90_P03420 (positions: 477-519)
Name: Fusion glycoprotein F0
Source organism: Human respiratory syncytial virus A
Length: 52 residues
Sequence:Sequence according to PDB SEQRESLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNK
UniProtKB AC: P11209 (positions: 158-209) Coverage: 9.1%
UniRef90 AC: UniRef90_P03420 (positions: 158-209)
Name: Fusion glycoprotein F0
Source organism: Human respiratory syncytial virus A
Length: 43 residues
Sequence:Sequence according to PDB SEQRESFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG
UniProtKB AC: P11209 (positions: 477-519) Coverage: 7.5%
UniRef90 AC: UniRef90_P03420 (positions: 477-519)
Name: Fusion glycoprotein F0
Source organism: Human respiratory syncytial virus A
Length: 52 residues
Sequence:Sequence according to PDB SEQRESLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNK
UniProtKB AC: P11209 (positions: 158-209) Coverage: 9.1%
UniRef90 AC: UniRef90_P03420 (positions: 158-209)
Name: Fusion glycoprotein F0
Source organism: Human respiratory syncytial virus A
Length: 43 residues
Sequence:Sequence according to PDB SEQRESFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAG
UniProtKB AC: P11209 (positions: 477-519) Coverage: 7.5%
UniRef90 AC: UniRef90_P03420 (positions: 477-519)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Complex evidence:
The subunits in the structure are bound via coiled coil interactions (PMID: 11106388). Coiled coils are highly versatile folding units (PMID: 11166216), where the formation of the structure and the interaction between subunits is almost ubiquitously linked. This cooperative nature of binding and folding that results in a two-step process has been demonstrated for coiled coils with varying oligomeric state from dimers (PMID: 9811815) and trimers (PMID: 10933510) up to heptamers (PMID: 17030805). While the interaction and folding are linked, in certain cases there can be significant residual structure before association (PMID: 8401212). However, these residual structural elements usually encompass 1-2 turns of helices that serve as a 'nucleation site' driving interaction and helix formation (zipping up) (PMID: 17438295), thus even in these cases monomeric coiled coil subunits cannot be considered to have a stable structure.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download our modified structure (.pdb)
