PDBsum entry 2c8i

Virus/receptor

PDB id: 2c8i

Contents

Protein chains

289 a.a.* *

252 a.a.* *

238 a.a.* *

60 a.a.* *

252 a.a.* *

* Residue conservation analysis

* C-alpha coords only

PDB id:

2c8i

Name:

Virus/receptor

Title:

Complex of echovirus type 12 with domains 1, 2, 3 and 4 of its receptor decay accelerating factor (cd55) by cryo electron microscopy at 16 a

Structure:

Echovirus 11 coat protein vp1. Chain: a. Echovirus 11 coat protein vp2. Chain: b. Echovirus 11 coat protein vp3. Chain: c. Echovirus 11 coat protein vp4. Chain: d. Other_details: structure of echovirus type 11 fitted into cryo-em

Source:

Human echovirus 11. Organism_taxid: 12078. Strain: gregory. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Authors:

D.M.Pettigrew,D.T.Williams,D.Kerrigan,D.J.Evans,S.M.Lea,D.Bhella

Key ref:

D.M.Pettigrew et al. (2006). Structural and functional insights into the interaction of echoviruses and decay-accelerating factor. J Biol Chem, 281, 5169-5177. PubMed id: 16272562 DOI: 10.1074/jbc.M510362200

Date:

05-Dec-05 Release date: 17-Jan-06

Protein chain

P29813  (POLG_EC11G) -  Genome polyprotein from Echovirus 11 (strain Gregory)

Seq: 2195 a.a.

Struc: 289 a.a.*

Protein chain

P29813  (POLG_EC11G) -  Genome polyprotein from Echovirus 11 (strain Gregory)

Seq: 2195 a.a.

Struc: 252 a.a.*

Protein chain

P29813  (POLG_EC11G) -  Genome polyprotein from Echovirus 11 (strain Gregory)

Seq: 2195 a.a.

Struc: 238 a.a.*

Protein chain

P29813  (POLG_EC11G) -  Genome polyprotein from Echovirus 11 (strain Gregory)

Seq: 2195 a.a.

Struc: 60 a.a.*

Protein chain

P08174  (DAF_HUMAN) -  Complement decay-accelerating factor from Homo sapiens

Seq: 381 a.a.

Struc: 252 a.a.*

* PDB and UniProt seqs differ at 41 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, B, C, D: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 2: Chains A, B, C, D: E.C.3.4.22.28 - picornain 3C.
• Reaction: Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 3: Chains A, B, C, D: E.C.3.4.22.29 - picornain 2A.
• Reaction: Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 4: Chains A, B, C, D: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M510362200

J Biol Chem 281:5169-5177 (2006)

PubMed id: 16272562

Structural and functional insights into the interaction of echoviruses and decay-accelerating factor.

D.M.Pettigrew, D.T.Williams, D.Kerrigan, D.J.Evans, S.M.Lea, D.Bhella.

ABSTRACT

Many enteroviruses bind to the complement control protein decay-accelerating factor (DAF) to facilitate cell entry. We present here a structure for echovirus (EV) type 12 bound to DAF using cryo-negative stain transmission electron microscopy and three-dimensional image reconstruction to 16-A resolution, which we interpreted using the atomic structures of EV11 and DAF. DAF binds to a hypervariable region of the capsid close to the 2-fold symmetry axes in an interaction that involves mostly the short consensus repeat 3 domain of DAF and the capsid protein VP2. A bulge in the density for the short consensus repeat 3 domain suggests that a loop at residues 174-180 rearranges to prevent steric collision between closely packed molecules at the 2-fold symmetry axes. Detailed analysis of receptor interactions between a variety of echoviruses and DAF using surface plasmon resonance and comparison of this structure (and our previous work; Bhella, D., Goodfellow, I. G., Roversi, P., Pettigrew, D., Chaudhry, Y., Evans, D. J., and Lea, S. M. (2004) J. Biol. Chem. 279, 8325-8332) with reconstructions published for EV7 bound to DAF support major differences in receptor recognition among these viruses. However, comparison of the electron density for the two virus.receptor complexes (rather than comparisons of the pseudo-atomic models derived from fitting the coordinates into these densities) suggests that the dramatic differences in interaction affinities/specificities may arise from relatively subtle structural differences rather than from large-scale repositioning of the receptor with respect to the virus surface.

Selected figure(s)

Figure 1.
FIGURE 1. Stereo views of surface-rendered three-dimensional reconstructions of unlabeled and DAF-labeled EV12. A, 14-Å resolution reconstruction of unlabeled EV12. B, reconstruction of EV12 bound to DAF[34] at 16-Å resolution showing clear density that we attribute to the two-domain receptor fragment; C, additional density seen in the 16-Å resolution reconstruction of EV12 bound to all four SCR domains of DAF.

Figure 2.
FIGURE 2. Calculation of a quasi-atomic model for EV12·DAF. A, variation in SCR2 orientation for the 14 crystal forms of DAF[1234], with each model superimposed onto the capsid-docked SCR3. Only SCR2 is shown for each model. B, variation in SCR2 orientation for the 43 different NMR models. C, the optimal SCR2 position is from chain B of the x-ray structure of Protein Data Bank code 1OK3 [PDB] . D, points of contact on DAF[1234] with the symmetry partner across the 2-fold axis. The green surface represents a steric clash between Arg^102 and Arg^103 and identical residues of the symmetry partner. This is resolved by side chain rearrangement. The blue surface is a van der Waals contact between Pro^137 and Pro^109 of the symmetry partner. The red and orange surfaces are an overlap between the main chain atoms of residues 174-180 of SCR3 (red) and a surface composed of residues 95-98 and 75-77 of the symmetry partner SCR2 (orange). This clash can be resolved only by a remodeling of loop 174-180. E, electron density of SCR1. The strong density at the center of each lobe is shown as a red mesh, whereas the lower contours are shown as a blue mesh. The major and minor lobes, as well as the position of SCR2, are highlighted. F, superposition of all 14 possible SCR1 orientations from the crystal structures. These orientations are consistent only with the minor lobe density. G, optimal "minor lobe" SCR1 model from the side. Also highlighted is the remodeled loop 174-180 on SCR3. H, complete DAF model based on a hybrid of the original DAF[34] fit (with the remodeled loop 174-180 on SCR3) and the two crystal structures that gave optimal SCR1 and SCR2 positions (green). Also shown in magenta is the alternative position for SCR1 proposed to explain the major lobe density. The symmetry partner DAF molecule is shown in red. I, radially depth-cued atomic model of the virus capsid (blue) decorated with 60 copies of the DAF[1234] hybrid model (green).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 5169-5177) copyright 2006.

Figures were selected by an automated process.