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January 20, 2017

Articles in Acta Cryst F

Crystallization and X-ray analysis of d-threonine aldolase from Chlamydomonas reinhardtii

Recombinant d-threonine aldolase from the green alga C. reinhardtii was purified to homogeneity and crystallized. An X-ray diffraction data set was collected to 1.85 Å resolution.

by Hirato et al. at January 20, 2017 08:12 AM

Crystal structure of the N-terminal anticodon-binding domain of the nondiscriminating aspartyl-tRNA synthetase from Helicobacter pylori

The crystal structure of the N-terminal anticodon-binding domain of the nondiscriminating aspartyl-tRNA synthetase from the human pathogen H. pylori was determined at a resolution of 2.0 Å. Two important turns (78GAGL81 and 83NPKL86), along with the conserved Pro84, are proposed to play a crucial role in the recognition of tRNAAsp and tRNAAsn.

by Songsiriritthigul et al. at January 20, 2017 08:12 AM

Expression and crystallographic studies of d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei

d-glycero-β-d-manno-Heptose-1-phosphate adenylyltransferase (HldC) from B. pseudomallei has been cloned, expressed, purified and crystallized. Synchrotron X-ray data from a selenomethionine-substituted HldC crystal were collected to 2.8 Å resolution.

by Park et al. at January 20, 2017 08:12 AM

Updates from ...

[Review] Human tissues in a dish: The research and ethical implications of organoid technology

The ability to generate human tissues in vitro from stem cells has raised enormous expectations among the biomedical research community, patients, and the general public. These organoids enable studies of normal development and disease and allow the testing of compounds directly on human tissue. Organoids hold the promise to influence the entire innovation cycle in biomedical research. They affect fields that have been subjects of intense ethical debate, ranging from animal experiments and the use of embryonic or fetal human tissues to precision medicine, organoid transplantation, and gene therapy. However, organoid research also raises additional ethical questions that require reexamination and potential recalibration of ethical and legal policies. In this Review, we describe the current state of research and discuss the ethical implications of organoid technology. Authors: Annelien L. Bredenoord, Hans Clevers, Juergen A. Knoblich

by Annelien L. Bredenoord at January 20, 2017 12:00 AM

[Research Article] Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler

Adenosine 5′-triphosphate (ATP)–dependent chromatin remodeling enzymes play essential biological roles by mobilizing nucleosomal DNA. Yet, how DNA is mobilized despite the steric constraints placed by the histone octamer remains unknown. Using methyl transverse relaxation–optimized nuclear magnetic resonance spectroscopy on a 450-kilodalton complex, we show that the chromatin remodeler, SNF2h, distorts the histone octamer. Binding of SNF2h in an activated ATP state changes the dynamics of buried histone residues. Preventing octamer distortion by site-specific disulfide linkages inhibits nucleosome sliding by SNF2h while promoting octamer eviction by the SWI-SNF complex, RSC. Our findings indicate that the histone core of a nucleosome is more plastic than previously imagined and that octamer deformation plays different roles based on the type of chromatin remodeler. Octamer plasticity may contribute to chromatin regulation beyond ATP-dependent remodeling. Authors: Kalyan K. Sinha, John D. Gross, Geeta J. Narlikar

by Kalyan K. Sinha at January 20, 2017 12:00 AM

[Research Article] Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy

Immunotherapies based on immune checkpoint blockade are highly effective in a subset of patients. An ongoing challenge is the identification of biomarkers that predict which patients will benefit from these therapies. Aneuploidy, also known as somatic copy number alterations (SCNAs), is widespread in cancer and is posited to drive tumorigenesis. Analyzing 12 human cancer types, we find that, for most, highly aneuploid tumors show reduced expression of markers of cytotoxic infiltrating immune cells, especially CD8+ T cells, and increased expression of cell proliferation markers. Different types of SCNAs predict the proliferation and immune signatures, implying distinct underlying mechanisms. Using published data from two clinical trials of immune checkpoint blockade therapy for metastatic melanoma, we found that tumor aneuploidy inversely correlates with patient survival. Together with other tumor characteristics such as tumor mutational load, aneuploidy may thus help identify patients most likely to respond to immunotherapy. Authors: Teresa Davoli, Hajime Uno, Eric C. Wooten, Stephen J. Elledge

by Teresa Davoli at January 20, 2017 12:00 AM

[Research Article] The role of dimer asymmetry and protomer dynamics in enzyme catalysis

Freeze-trapping x-ray crystallography, nuclear magnetic resonance, and computational techniques reveal the distribution of states and their interconversion rates along the reaction pathway of a bacterial homodimeric enzyme, fluoroacetate dehalogenase (FAcD). The crystal structure of apo-FAcD exhibits asymmetry around the dimer interface and cap domain, priming one protomer for substrate binding. This asymmetry is dynamically averaged through conformational exchange on a millisecond time scale. During catalysis, the protomer conformational exchange rate becomes enhanced, the empty protomer exhibits increased local disorder, and water egresses. Computational studies identify allosteric pathways between protomers. Water release and enhanced dynamics associated with catalysis compensate for entropic losses from substrate binding while facilitating sampling of the transition state. The studies provide insights into how substrate-coupled allosteric modulation of structure and dynamics facilitates catalysis in a homodimeric enzyme. Authors: Tae Hun Kim, Pedram Mehrabi, Zhong Ren, Adnan Sljoka, Christopher Ing, Alexandr Bezginov, Libin Ye, Régis Pomès, R. Scott Prosser, Emil F. Pai

by Tae Hun Kim at January 20, 2017 12:00 AM

[Editorial] Everyone should try

The new year brings opportunities to think creatively about finding solutions to difficult problems. It's a chance to affirm that although views may differ dramatically, we should try to work effectively with one another. My namesake believed in this. Jeremy Stone, the long-time president of the Federation of American Scientists, passed away on 1 January at the age of 81. As a graduate student, Stone attended mathematics classes taught by my father, and he and his wife Betty Jane (B.J.) Stone, also a distinguished mathematician and statistician, babysat my brother and me. Stone's career followed a remarkable and unusual path for a scientist—indeed, for anyone—and highlights how individuals with training in science, technology, engineering, and mathematics can contribute to society in diverse and profound ways. Author: Jeremy Berg

by Jeremy Berg at January 20, 2017 12:00 AM

[In Brief] News at a glance

In science news around the world, the United States confers protections to the Walrus Islands and a handful of other sites of archaeological significance by making them historic landmarks, a U.S. report finds that marijuana can treat chronic pain and notes that researchers who want to study the drug face significant obstacles, a new international particle accelerator located in Jordan takes a big step forward by achieving its first circulating beam of electrons, a U.K. study gives the go-ahead to build the world's first tidal lagoon power plant in the country, and more. Also, scientists express anger at the suggestion that U.S. President-elect Donald Trump might create a "vaccine safety" commission that could focus on scientifically discredited links between vaccines and autism. And a video game helps researchers understand how flocks of starlings keep predators at bay.

January 20, 2017 12:00 AM