Mechanism of Na+/H+ antiporting

Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model.     

Intellectual property. Enhanced: intellectual property landscape of the human genome

The impact of gene patents on downstream research and innovation are unknown, in part because of a lack of empirical data on the extent and nature of gene patenting. In this Policy Forum, the authors show that 20% of human gene DNA sequences are patented and that some genes are patented as many as 20 times. Unsurprisingly, genes associated with health and disease are more patented than the genome at large. The intellectual property rights for some genes can become highly fragmented between many owners, which suggests that downstream innovators may face considerable costs to gain access to gene-oriented technologies.     

Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling

The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.     

Dynamic complex formation during the yeast cell cycle

To analyze the dynamics of protein complexes during the yeast cell cycle, we integrated data on protein interactions and gene expression. The resulting time-dependent interaction network places both periodically and constitutively expressed proteins in a temporal cell cycle context, thereby revealing previously unknown components and modules. We discovered that most complexes consist of both periodically and constitutively expressed subunits, which suggests that the former control complex activity by a mechanism of just-in-time assembly. Consistent with this, we show that additional regulation through targeted degradation and phosphorylation by Cdc28p (Cdk1) specifically affects the periodically expressed proteins.     

Accumulation of trehalose in the thermophilic fungus Chaetomium thermophilum var. coprophilum in response to heat or salt stress

The disaccharide trehalose, known to be an effective protectant against various kinds of stress, was observed to accumulate in the cytosol of Chaetomium thermophilum var. coprophilum during heat stress. Trehalose was apparently neither involved in the defence of C. thermophilum var. coprophilum against high concentrations of sodium chloride nor directly linked to thermophily.In C. thermophilum var. coprophilum three different trehalose hydrolyzing activities were eluted from a mono Q anion exchange column by sodium chloride concentrations of 0.10, 0.15 and 0.24 M, respectively.