Finessing Crystal Analysis: Protein crystallography has revolutionized our understanding of a whole variety of biological processes (see the Perspective by Evans ). In crystallography, the measure of agreement between the data and the calculated model is not on the same scale as the measure of data quality, making it challenging to choose an optimal high resolution limit beyond which the data should be discarded. Now, Karplus and Diederichs (p. 1030 ) introduce a statistical model that assesses agreement of model and data accuracy on the same scale. Determining the structures of biological macromolecules by x-ray crystallography requires solving the phase problem. The two techniques that dominate phase evaluation (multi- and single-wavelength anomalous diffraction) rely on element-specific scattering from incorporated heavy atoms. Liu et al. (p. 1033 ) present procedures for routine structure determination of native proteins with no heavy atom incorporation. The technique, which relies on combining data from multiple crystals, was used to determine the structures of four native proteins, including a 1200-residue complex.

Eukaryotic 2-Cys peroxiredoxins (2-Cys Prxs) not only act as antioxidants, but also appear to regulate hydrogen peroxide–mediated signal transduction. We showthat bacterial 2-Cys Prxs are much less sensitive to oxidative inactivation than are eukaryotic 2-Cys Prxs. By identifying two sequence motifs unique to the sensitive 2-Cys Prxs and comparing the crystal structure of a bacterial 2-Cys Prx at 2.2 angstrom resolution with other Prx structures, we define the structural origins of sensitivity. We suggest this adaptation allows 2-Cys Prxs to act as floodgates, keeping resting levels of hydrogen peroxide low, while permitting higher levels during signal transduction.

The quantity R_sym (also called R_merge) is almost universally used for describing X-ray diffraction data quality. Here, we prove that R_sym is seriously flawed, because it has an implicit dependence on the redundancy of the data. A corrected R-factor, R_meas, is introduced as the equivalent robust indicator of data consistency. In addition, we introduce R_mrgd, an R-factor that reflects the gain in accuracy upon averaging of equivalent reflections, as a useful indicator of the quality of reduced data. These new data quality indicators better reveal the benefits of highly redundant data and should stimulate improvements in data quality through increased merging of data from multiple crystals.

The ezrin-radixin-moesin (ERM) protein family link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain, a common membrane binding module. ERM proteins are regulated by an intramolecular association of the FERM and C-terminal tail domains that masks their binding sites. The crystal structure of a dormant moesin FERM/tail complex reveals that the FERM domain has three compact lobes including an integrated PTB/PH/ EVH1 fold, with the C-terminal segment bound as an extended peptide masking a large surface of the FERM domain. This extended binding mode suggests a novel mechanism for how different signals could produce varying levels of activation. Sequence conservation suggests a similar regulation of the tumor suppressor merlin.