In This Issue

1031 Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens function

A. Laganowsky, J. L. P. Benesch, M. Landau, L. Ding, M. R. Sawaya, D. Cascio, Q. Huang, C. V. Robinson, J. Horwitz, and D. Eisenberg

Despite the enormously high protein concentration in the eye lens, crystallin proteins have evolved to maintain transparency. Crystal structures of truncated Alpha crystallins reveal how these molecules evolved to prevent crystallization, which would diminish transparency. An encoded palindromic C-terminal tail causes bi-directional intermolecular binding. Also promiscuous beta sheet dimer interaction is created with three distinct registration states. Together these structural mechanisms create polymorophic interactions, preventing crystallization, and preserving eye lens function.

944 Internal motion in protein crystal structures

A. Schmidt and V. S. Lamzin

Crystallography has long been established as the method of choice for detailed structural investigation of biological macromolecules. However, at least for macromolecules the results were always considered “static,” presenting only one snapshot of a molecular conformation. At very high resolution this snapshot is very accurate and contains a wealth of structural detail. In addition, it offers the means to extract information on the preferred directions of motion within a molecule from anisotropic atomic displacement parameters. Schmidt and Lamzin developed a method of deriving molecular fragments from the patterns of motion based on single X-ray structures and could trace the subtle effects of ligand binding or pH change.

974 Structural and functional analysis of the phosphoryl transfer reaction mediated by the human small C-terminal domain phosphatase, Scp1

M. Zhang, J. Liu, Y. Kim, J. E. Dixon, S. L. Pfaff, G. N. Gill, J. P. Noel, and Y. Zhang

Human small C-terminal domain phosphatase 1 (Scp1) modulates the phosphorylation state of the C-terminal domain (CTD) of eukaryotic RNA polymerase II (RNAP II), and has been identified as a conserved regulator of neuronal stem cell development. Scp1 is a member of haloacid dehalogenase (HAD) superfamily, whose catalysis depends on a Mg²⁺ ion and a Asp-X-Asp-X-(Thr/Val) motif. The first Asp of the motif is identified as the nucleophile that is subject to phosphorylation leading to a phosphoryl-aspartate intermediate. This high-energy mixed anhydride intermediate is subsequently hydrolyzed to regenerate the enzyme. Here, Zhang, et al. captured the snapshots of the phosphoryl transfer reaction at each stage of Scp1-mediated catalysis. Through structural-based sequence alignment, they show that the spatial position of the Asp206 side chain is strictly conserved throughout HAD family, strongly suggesting that Asp206 and its equivalent residues in other HAD family members play important structural and possible mechanistic roles.

1091 Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA

L. J. Worrall, M. Vuckovic, and N. C. J. Strynadka

Worrall, et al. report the novel high resolution crystal structure of the C-terminal domain of InvA, a prominent inner-membrane component of the Salmonella type III secretion system (T3SS) apparatus. The overall structure is of novel architecture consisting of four subdomains. Of notable interest, an observed similarity between one subdomain and the ATPase binding peripheral stalk from the A/V-type ATPases—which share some features in common with the T3SS export apparatus—may shed some light on how the InvA family mediates docking of the soluble effector loaded ATPase export complex prior to protein translocation. The study expands on the structural knowledge of the conserved inner-membrane components of the T3SS and will contribute valuable information to the functional understanding of these complex molecular nano-machines.