PDBsum entry 3bbz

Viral protein, replication

PDB id: 3bbz

Contents

Protein chains

48 a.a.

Ligands

FMT ×6

Metals

_BR ×2

Waters ×52

PDB id:

3bbz

Name:

Viral protein, replication

Title:

Structure of the nucleocapsid-binding domain from the mumps virus phosphoprotein

Structure:

P protein. Chain: a, b. Fragment: nucleocapsid-binding domain, unp residues 343-391. Synonym: phosphoprotein. Engineered: yes. Mutation: yes

Source:

Mumps virus. Organism_taxid: 11161. Strain: jeryl-lynn vaccine. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.193 R-free: 0.241

Authors:

R.L.Kingston,L.S.Gay,W.S.Baase,B.W.Matthews

Key ref:

R.L.Kingston et al. (2008). Structure of the nucleocapsid-binding domain from the mumps virus polymerase; an example of protein folding induced by crystallization. J Mol Biol, 379, 719-731. PubMed id: 18468621 DOI: 10.1016/j.jmb.2007.12.080

Date:

11-Nov-07 Release date: 27-May-08

Protein chains

Q9J4L6  (Q9J4L6_MUMPJ) -  Phosphoprotein from Mumps virus (strain Jeryl-Lynn)

Seq: 391 a.a.

Struc: 48 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.jmb.2007.12.080

J Mol Biol 379:719-731 (2008)

PubMed id: 18468621

Structure of the nucleocapsid-binding domain from the mumps virus polymerase; an example of protein folding induced by crystallization.

R.L.Kingston, L.S.Gay, W.S.Baase, B.W.Matthews.

ABSTRACT

The human pathogen mumps virus, like all paramyxoviruses, encodes a polymerase responsible for virally directed RNA synthesis. The template for the polymerase is the nucleocapsid, a filamentous protein-RNA complex harboring the viral genome. Interaction of the polymerase and the nucleocapsid is mediated by a small domain tethered to the end of the phosphoprotein (P), one of the polymerase subunits. We report the X-ray crystal structure of this region of mumps virus P (the nucleocapsid-binding domain, or NBD, amino acids 343-391). The mumps P NBD forms a compact bundle of three alpha-helices within the crystal, a fold apparently conserved across the Paramyxovirinae. In solution, however, the domain exists in the molten globule state. This is demonstrated through application of differential scanning calorimetry, circular dichroism spectroscopy, NMR spectroscopy, and dynamic light scattering. While the mumps P NBD is compact and has persistent secondary structure, it lacks a well-defined tertiary structure under normal solution conditions. It can, however, be induced to fold by addition of a stabilizing methylamine cosolute. The domain provides a rare example of a molten globule that can be crystallized. The structure that is stabilized in the crystal represents the fully folded state of the domain, which must be transiently realized during binding to the viral nucleocapsid. While the intermolecular forces that govern the polymerase-nucleocapsid interaction appear to be different in measles, mumps, and Sendai viruses, for each of these viruses, polymerase translocation involves the coupled binding and folding of protein domains. In all cases, we suggest that this will result in a weak-affinity protein complex with a short lifetime, which allows the polymerase to take rapid steps forward.

Selected figure(s)

Figure 1.
Fig. 1. The structure of the mumps P NBD. (a) Schematic ribbon diagram showing the arrangement of the α-helices. (b) Representative electron density within the crystal. The map is a 2m|F[o]| − D|F[c]| (SigmaA weighted) Fourier synthesis. (c) Aligned C^α plots of the mumps, measles, and Sendai virus NBDs.

Figure 6.
Fig. 6. Close-packed layers of the mumps P NBD formed within the crystal. (a) Schematic ribbon diagram showing the packing arrangement of molecules in the xy-plane of the crystal. The two molecules within the asymmetric unit are shown in light blue. Symmetry-equivalent molecules are shown in gray. For clarity, only a single molecular layer is shown. As depicted, the noncrystallographic twofold rotation axis lies parallel with the crystallographic z-axis. (b) A molecular (Connolly) surface representation of the region shown in (a) calculated using the program PyMOL.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 379, 719-731) copyright 2008.

Figures were selected by the author.