In This Issue

1941 Twists and turns in ubiquitin-like protein conjugation cascades

Brenda A. Schulman

Post-translational modification by ubiquitin-like proteins (UBLs) is a primary eukaryotic means of protein regulation. This highly dynamic, multistep, multienzyme process involves sequential transport of an entire protein—the UBL—between multiple enzyme active sites within an E1 enzyme, then, transiently onto an E2 enzyme, and ultimately with assistance of an E3 enzyme onto a target protein. The structures and interactions of E1, E2, and E3 enzymes are themselves dynamic, and plasticity of enzyme conformations—from wholesale domain rotations to complete remodeling of portions of structures—helps mediate UBL ligation to targets in a specific manner. This review highlights some recent glimpses into enzyme dynamics in UBL modification pathways.

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1955 Fractal dimension of an intrinsically disordered protein: Small-angle X-ray scattering and computational study of the bacteriophage λ N protein

Daniel Johansen, Jill Trewhella, David P. Goldenberg

With the recent recognition that the functional forms of many proteins may be partially or fully unfolded, there is now great interest in characterizing the physical properties of these intrinsically disordered proteins (IDPS). Johansen et al. have used small-angle X-ray scattering (SAXS) and computational modeling to characterize one such protein, a transcriptional antitermination factor encoded by the bacteriophage lambda. In addition to measuring the average radius of gyration, the authors have determined the mass fractal dimension, which is a measure of the average internal density of the molecules and their propensity to interact with solvent. The use of SAXS to measure the fractal dimension is well established in the study of synthetic polymers, but has only recently been applied to unfolded proteins. In the present study, the analysis demonstrates that the lambda N protein behaves as an expanded and well-solvated random coil, properties that may facilitate its function in the dynamic transcription complex.

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2125 SARS-CoV heptad repeat 2 is a trimer of parallel helices

Jessica Celigoy, Benjamin Ramirez, Michael Caffrey

Heptad repeat 2 of viral envelope proteins plays a critical role in the entry of many viruses including those of HIV, influenza and SARS-CoV. Interestingly, the structure of this domain determined by X-ray crystallography is different from that determined by NMR spectroscopy. In this work, Caffrey and co-workers examine the differences between the X-ray and NMR structures. Their new data suggests that the differences between the structures is due to the presence of nine native residues in the NMR construct, which supports the relevance of the parallel trimer model of heptad repeat 2.

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1982 Structural cooperativity in histone H3 tail modifications

Deniz Sanli, Ozlem Keskin, Attila Gursoy, Burak Erman

Post-translational modifications of histone tails have crucial roles in regulation of cellular processes. There is cross-regulation between the modifications of K4, K9, and K14 residues. This study shows structural changes of the histone H3 tail originating from the three most important modifications; tri-methylation of K4 and K9, and acetylation of K14 with molecular dynamics. It discusses the consequences of these results on the binding modes and specificity of the histone modifying enzymes.

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