PDBsum entry 1vps

Viral protein

PDB id: 1vps

Contents

Protein chains

285 a.a. *

Ligands

NAG-GAL-SIA-SIA ×5

Waters ×2127

* Residue conservation analysis

References listed in PDB file

Key reference

Title

High-Resolution structure of a polyomavirus vp1-Oligosaccharide complex: implications for assembly and receptor binding.

Authors

T.Stehle, S.C.Harrison.

Ref.

EMBO J, 1997, 16, 5139-5148. [DOI no: 10.1093/emboj/16.16.5139]

PubMed id

9305654

Abstract

The crystal structure of a recombinant polyomavirus VP1 pentamer (residues 32-320) in complex with a branched disialylated hexasaccharide receptor fragment has been determined at 1.9 A resolution. The result extends our understanding of oligosaccharide receptor recognition. It also suggests a mechanism for enhancing the fidelity of virus assembly. We have previously described the structure of the complete polyomavirus particle complexed with this receptor fragment at 3.65 A. The model presented here offers a much more refined view of the interactions that determine carbohydrate recognition and allows us to assign additional specific contacts, in particular those involving the (alpha2,6)-linked, branching sialic acid. The structure of the unliganded VP1 pentamer, determined independently, shows that the oligosaccharide fits into a preformed groove and induces no measurable structural rearrangements. A comparison with assembled VP1 in the virus capsid reveals a rearrangement of residues 32-45 at the base of the pentamer. This segment may help prevent the formation of incorrectly assembled particles by reducing the likelihood that the C-terminal arm will fold back into its pentamer of origin.

Figure 2.
Figure 2 Difference Fourier electron density, in stereo, for the oligosaccharide, calculated at 2.0 Å resolution and contoured at 2.5 . Figure prepared with O (Jones et al., 1991).

Figure 3.
Figure 3 The carbohydrate binding site of VP1. (A) Schematic view of the interactions. Hydrogen bonds are represented by thin broken lines, and hydrophobic contacts are shown as thick gray broken lines. Asp85#, located at the tip of the BC2-loop of the clockwise VP1 neighbor, approaches the N-acetyl group of NeuNAc-1. The small circles labeled 'W' represent water molecules. (B) Top view of the binding surface of VP1, showing the groove that accommodates NeuNAc-1–( 2,3)–Gal and the shallow pocket for NeuNAc-2. The yellow arrow indicates the attachment site for additional sugars. The surface has been calculated with MS (Connolly, 1983) using a probe radius of 1.4 Å. (C) View into the carbohydrate binding site, showing the interactions with the NeuNAc-1–( 2,3)–Gal moiety. (D) Interactions as in (C), with the viewpoint rotated by 90°, so that we are looking along the oligosaccharide chain from its sialic-acid end. (E) Interactions with NeuNAc-2. In panels (C–E), residues that form hydrogen bonds with the carbohydrate are colored orange and residues that form hydrophobic contacts, magenta. Residues that do not directly contact the carbohydrate are shown in gray. Water molecules are represented with green spheres and hydrogen bonds are shown as broken lines. Figure prepared with RIBBONS (Carson, 1987) (panels A, C, D and E) and O (Jones et al., 1991) (panel B).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 5139-5148) copyright 1997.

Secondary reference #1

Title

The structure of simian virus 40 refined at 3.1 a resolution.

Authors

T.Stehle, S.J.Gamblin, Y.Yan, S.C.Harrison.

Ref.

Structure, 1996, 4, 165-182. [DOI no: 10.1016/S0969-2126(96)00020-2]

PubMed id

8805523

Figure 4.
Figure 4. Schematic illustration of the β-sheets of VP1. A strand contributed by another monomer is shown in black. Hydrogen bonds are shown as solid lines and polypeptide chain connections between sheets are shown by dotted lines. Figure 4. Schematic illustration of the β-sheets of VP1. A strand contributed by another monomer is shown in black. Hydrogen bonds are shown as solid lines and polypeptide chain connections between sheets are shown by dotted lines.

Figure 10.
Figure 10. The calcium-binding sites of SV40. (a) Ribbon diagram of two SV40 VP1 monomers, shown in light and dark gray. The invading arms are shown in magenta and yellow. The calcium ions are represented by green spheres. (b) Close-up view of the binding sites. Residues whose side chains could contact the ions are shown in atomic detail. Figure 10. The calcium-binding sites of SV40. (a) Ribbon diagram of two SV40 VP1 monomers, shown in light and dark gray. The invading arms are shown in magenta and yellow. The calcium ions are represented by green spheres. (b) Close-up view of the binding sites. Residues whose side chains could contact the ions are shown in atomic detail. (Figure generated with RIBBONS [[4]67].)

The above figures are reproduced from the cited reference with permission from Cell Press

Secondary reference #2

Title

Crystal structures of murine polyomavirus in complex with straight-Chain and branched-Chain sialyloligosaccharide receptor fragments.

Authors

T.Stehle, S.C.Harrison.

Ref.

Structure, 1996, 4, 183-194. [DOI no: 10.1016/S0969-2126(96)00021-4]

PubMed id

8805524

Figure 1.
Figure 1. Chemical structures of the two polyoma ligands: (a) 3′-sialyl lactose, a representative of straight-chain receptor fragments, used in complex-1; (b) the branched-chain oligosaccharide in complex-2. Figure 1. Chemical structures of the two polyoma ligands: (a) 3′-sialyl lactose, a representative of straight-chain receptor fragments, used in complex-1; (b) the branched-chain oligosaccharide in complex-2.

Figure 8.
Figure 8. Molecular surfaces of polyoma and SV40 pentamers. (a) Surface of a polyomavirus pentamer with the 5-fold symmetry axis indicated. The branched-chain ligand of complex-2 is shown as a ball-and-stick model. The two terminal sugars are not shown. The surface has four pockets. The NeuNAc-(α2,3)-Gal moiety occupies pockets 1 and 2, the (α2,6)-linked NeuNAc occupies pocket 3. (b) SV40 surface. The surface is surprisingly similar to that of polyoma, and the view shows that there are pockets at roughly similar positions. Figure 8. Molecular surfaces of polyoma and SV40 pentamers. (a) Surface of a polyomavirus pentamer with the 5-fold symmetry axis indicated. The branched-chain ligand of complex-2 is shown as a ball-and-stick model. The two terminal sugars are not shown. The surface has four pockets. The NeuNAc-(α2,3)-Gal moiety occupies pockets 1 and 2, the (α2,6)-linked NeuNAc occupies pocket 3. (b) SV40 surface. The surface is surprisingly similar to that of polyoma, and the view shows that there are pockets at roughly similar positions. (Figure produced with GRASP [[4]38].)

The above figures are reproduced from the cited reference with permission from Cell Press

Secondary reference #3

Title

Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment.

Authors

T.Stehle, Y.Yan, T.L.Benjamin, S.C.Harrison.

Ref.

Nature, 1994, 369, 160-163.

PubMed id

8177322