ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacterium Ramlibacter tataouinensis . RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, the R. tataouinensis bacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR from Agrobacterium tumefaciens , crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon ) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCE BphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction.
more »
« less
Are we ready for broader adoption of ARM in the HPC community: Performance and Energy Efficiency Analysis of Benchmarks and Applications Executed on High-End ARM Systems
More Like this
-
-
ARM servers are becoming increasingly common, making server technologies such as virtualization for ARM of growing importance. We present the first study of ARM virtualization performance on server hardware, including multi-core measurements of two popular ARM and x86 hypervisors, KVM and Xen. We show how ARM hardware support for virtualization can enable much faster transitions between VMs and the hypervisor, a key hypervisor operation. However, current hypervisor designs, including both Type 1 hypervisors such as Xen and Type 2 hypervisors such as KVM, are not able to leverage this performance benefit for real application workloads on ARMv8.0. We discuss the reasons why and show that other factors related to hypervisor software design and implementation have a larger role in overall performance. Based on our measurements, we discuss software changes and new hardware features, the Virtualization Host Extensions (VHE), added in ARMv8.1 that bridge the gap and bring ARM's faster VM-to-hypervisor transition mechanism to modern Type 2 hypervisors running real applications.more » « less
-
more » « less
This essay considers how racial paradigms in the United States produce white subjectivity as part of a broader structure of policing Blackness that becomes bureaucratically encoded through law enforcement agents and their discursive practices. Given this, it is not unexpected that the figure of the “Karen” and agents of law enforcement police similar behaviors and figures, given they embody the same ethos of white supremacy, differentiated largely by virtue of the bureaucratic structures in place to direct, reproduce, and legitimate anti‐Blackness within an institutional framework.
-
We propose a new variant of the top arm identification problem, top feasible arm identification, where there are K arms associated with D-dimensional distributions and the goal is to find m arms that maximize some known linear function of their means subject to the constraint that their means belong to a given set P € R D. This problem has many applications since in many settings, feedback is multi-dimensional and it is of interest to perform constrained maximization. We present problem-dependent lower bounds for top feasible arm identification and upper bounds for several algorithms. Our most broadly applicable algorithm, TF-LUCB-B, has an upper bound that is loose by a factor of OpDlogpKqq. Many problems of practical interest are two dimensional and, for these, it is loose by a factor of OplogpKqq. Finally, we conduct experiments on synthetic and real-world datasets that demonstrate the effectiveness of our algorithms. Our algorithms are superior both in theory and in practice to a naive two-stage algorithm that first identifies the feasible arms and then applies a best arm identification algorithm to the feasible arms.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1145/3581576.3581618
