In this issue
In this issue
693 A decade and a half of protein intrinsic disorder: Biology still waits for physics
Vladimir N. Uversky
Recent years witnessed an increased appreciation of the abundance and multifarious functionality of intrinsically disordered proteins (IDPs). They lack stable structure under physiological conditions in vitro existing instead as dynamic conformational ensembles often resembling 'protein clouds'. The functional repertoire of IDPs is complementary to that of ordered proteins. IDPs are promiscuous binders that commonly involved in regulation, signaling and control pathways. IDPs are tightly controlled and regulated (e.g., by binding to specific partners, posttranslational modifications, or via alternative splicing). Numerous IDPs are associated with a wide range of human diseases, including most devastating maladies such as cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, diabetes, etc. which makes IDPs novel, very attractive, but difficult, drug targets.
800 The three-dimensional structure of TrmB, a transcriptional regulator of dual function in the hyperthermophilic archaeon Pyrococcus furiosus in complex with sucrose
Michael Krug, Sung-Jae Lee, Winfried Boos, Kay Diederichs and Wolfram Welte
TrmB controls transcription from two different operons by adopting different conformations dependent on the bound effector molecule. Maltose abrogates repression of the TM (trehalose/maltose) but increases repression of the MD (maltodextrin) operon whereas sucrose does the opposite. The conformations of TrmB in complex with the respective operator sequences thus must be different as is corroborated by mutational data. Here the structure of TrmB with bound sucrose is reported which seems to be poised for TM operator binding. It is a dimer showing two symmetrical winged HTH motives. Dimerization occurs via a coiled-coil.
677 Structural analyses of the pre-mRNA splicing machinery
Lingdi Zhang, Xueni Li and Rui Zhao
Pre-mRNA splicing is a critical event in the gene expression pathway of all eukaryotes. The splicing reaction is catalyzed by the spliceosome, a huge protein-RNA complex that contains five snRNAs and hundreds of different protein factors. Although the highly dynamic nature of the spliceosome, in both composition and conformation, posed daunting challenges to structural studies, there has been significant recent progress on structural analyses of the splicing machinery, using electron microscopy, crystallography, and NMR. These findings significantly advanced our understanding of the structure and function of the splicing machinery.
762 Structural characterisation of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target
Nicole R. Pendini, Min Y. Yap, Steven W. Polyak, Nathan P. Cowieson, Andrew Abell, Grant W. Booker, John C. Wallace, Jacqueline A. Wilce and Matthew C. J. Wilce
The emergence of antibiotic resistance prompts the characterisation of potential new drug targets in pathogenic bacteria. Biotin protein ligase from Staphylococcus aureus (SaBPL) is an essential protein that transfers biotin via the biotin carrier coupling protein (BCCP) domain of metabolic enzymes that require CO2. It is also a transcriptional repressor that serves to limit biotin synthesis. Using X-ray crystallography and small angle X-ray scattering we have been able to resolve details of the molecular structure of SaBPL as well as its interactions with biotin-ATP, BCCP and DNA binding partners. This data will assist in the design of new antibiotics that target BPL.