title: Coiled-coil deformations in crystal structures: the measles virus phosphoprotein multimerization domain as an illustrative example.
abstract: The structures of two constructs of the measles virus (MeV) phosphoprotein (P) multimerization domain (PMD) are reported and are compared with a third structure published recently by another group [Communie et al. (2013), J. Virol. 87, 7166-7169]. Although the three structures all have a tetrameric and parallel coiled-coil arrangement, structural comparison unveiled considerable differences in the quaternary structure and unveiled that the three structures suffer from significant structural deformation induced by intermolecular interactions within the crystal. These results show that crystal packing can bias conclusions about function and mechanism based on analysis of a single crystal structure, and they challenge to some extent the assumption according to which coiled-coil structures can be reliably predicted from the amino-acid sequence. Structural comparison also highlighted significant differences in the extent of disorder in the C-terminal region of each monomer. The differential flexibility of the C-terminal region is also supported by size-exclusion chromatography and small-angle X-ray scattering studies, which showed that MeV PMD exists in solution as a dynamic equilibrium between two tetramers of different compaction. Finally, the possible functional implications of the flexibility of the C-terminal region of PMD are discussed.
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Blocquel
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: Johnny
authors.initials: J
authors.lastname: Habchi
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Durand
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Sevajol
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Ferron
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: Jenny
authors.initials: J
authors.lastname: Erales
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Papageorgiou
authors.affiliation: Aix-Marseille University, AFMB UMR 7257, 13288 Marseille, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Longhi
mesh_terms: D001704:Biopolymers / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D008459:Measles virus / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry*; D011487:Protein Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D001704:Biopolymers; D010750:Phosphoproteins; D014764:Viral Proteins
keywords: coiled coils; measles virus phosphoprotein multimerization domain