PDBsum entry 1kqr

Viral protein

PDB id: 1kqr

Contents

Protein chain

160 a.a. *

Ligands

SO4

MNA

GOL

Waters ×190

* Residue conservation analysis

PDB id:

1kqr

Name:

Viral protein

Title:

Crystal structure of the rhesus rotavirus vp4 sialic acid binding domain in complex with 2-o-methyl-alpha-d-n-acetyl neuraminic acid

Structure:

Vp4. Chain: a. Fragment: sialic acid binding domain (residues 62-224). Engineered: yes

Source:

Rhesus rotavirus. Organism_taxid: 10969. Gene: segment 4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.40Å R-factor: 0.169 R-free: 0.181

Authors:

P.R.Dormitzer,Z.-Y.J.Sun,G.Wagner,S.C.Harrison

Key ref:

P.R.Dormitzer et al. (2002). The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J, 21, 885-897. PubMed id: 11867517 DOI: 10.1093/emboj/21.5.885

Date:

07-Jan-02 Release date: 27-Mar-02

Protein chain

P12473  (VP4_ROTRH) -  Outer capsid protein VP4 from Rotavirus A (strain RVA/Monkey/United States/RRV/1975/G3P5B[3])

Seq: 776 a.a.

Struc: 160 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1093/emboj/21.5.885

EMBO J 21:885-897 (2002)

PubMed id: 11867517

The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site.

P.R.Dormitzer, Z.Y.Sun, G.Wagner, S.C.Harrison.

ABSTRACT

Cell attachment and membrane penetration are functions of the rotavirus outer capsid spike protein, VP4. An activating tryptic cleavage of VP4 produces the N-terminal fragment, VP8*, which is the viral hemagglutinin and an important target of neutralizing antibodies. We have determined, by X-ray crystallography, the atomic structure of the VP8* core bound to sialic acid and, by NMR spectroscopy, the structure of the unliganded VP8* core. The domain has the beta-sandwich fold of the galectins, a family of sugar binding proteins. The surface corresponding to the galectin carbohydrate binding site is blocked, and rotavirus VP8* instead binds sialic acid in a shallow groove between its two beta-sheets. There appears to be a small induced fit on binding. The residues that contact sialic acid are conserved in sialic acid-dependent rotavirus strains. Neutralization escape mutations are widely distributed over the VP8* surface and cluster in four epitopes. From the fit of the VP8* core into the virion spikes, we propose that VP4 arose from the insertion of a host carbohydrate binding domain into a viral membrane interaction protein.

Selected figure(s)

Figure 1.
Figure 1 The rotavirus triple-layered virion. VP4 and VP7 make up the outer capsid, which constitutes the entry apparatus. The RNA, VP2 and VP6 are the major structural components of the double-layered particle, which is the transcriptionally active core. The line drawing is based on an electron cryomicroscopy-based reconstruction (Yeager et al., 1990).

Figure 6.
Figure 6 Surface representations of the rotavirus VP8^* core, colored according to the variability between the rotavirus strains listed in Table III. Blue represents the most conserved surfaces and red represents the most variable surfaces. Labeled amino acids indicate neutralization escape mutations (Table IV). Labels colored by epitope: 8-1, green; 8-2, blue; 8-3, yellow; 8-4, pink; and not assigned, black. (A) As viewed along arrow 3 of Figure 7. (B) As viewed along arrow 1 and in panel B of Figure 7. (C) As viewed along arrow 2 and in panel C of Figure 7. (A) and (C) are rotated 90° in either direction around the horizontal axis relative to (B), as indicated by arrows on the figure.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 885-897) copyright 2002.

Figures were selected by an automated process.