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New World hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The structure of Machupo virus surface glycoprotein 1 bound to the human transferrin receptor 1 is now presented by Harrison and colleagues. The structure resembles a butterfly, shown in the cover photograph by Richard Mann. pp pp 438–444
Your paper went out to review, and after anxious waiting, you receive the letter asking for a revised paper. However, those ever-demanding editors and reviewers want more. One of the most important elements of a revision is the point-by-point response. Here are some tips for making it more effective.
The tumor suppressor p53 protects the cell from cellular stress, and in so doing it decides between cell-cycle arrest and cell death. The high-resolution structure of four DNA binding domains of p53 in complex with DNA shows how the structural collaboration between protein and DNA may influence the biological outcomes of the tumor suppressor.
Eukaryotic cells have numerous non–membrane bound bodies whose functions are often unclear. On page 403 of this issue, Strzelecka and colleagues provide evidence that the ability to form Cajal bodies increases the rate of small nuclear ribonucleoprotein (snRNP) biogenesis and/or function. This supports the hypothesis that some cellular bodies form to increase the rates of assembly of multicomponent cellular machines.
Two recent papers break major new ground on the issues of NHEJ, backup pathways for NHEJ and how these relate to the chromosomal translocation process.
In this issue, a long-awaited report sheds new light on the strange performance of bacterial flagellar filaments. We now have high-resolution data on two different, 'switched' versions of the structure.
Eph receptors are cell surface protein tyrosine kinases that mediate cell-cell communication. The crystal structure of the full ectodomain of unliganded human EphA2 (eEphA2) reveals that it forms linear arrays of staggered, parallel receptors, whereas that of eEphA2 in complex with ephrinA5 forms a more elaborate assembly with interfaces that are crucial for localization at cell-cell contacts and for activation-dependent degradation.
The function of many non-membrane bound aggregates (Cajal bodies, P-bodies, stress granules, etc.) is poorly understood. Now studies in zebrafish embryos show that coilin promotes spliceosomal small nuclear ribonucleoproteins (snRNPs) assembly, most likely by concentrating snRNP components in Cajal bodies and to overcome a rate-limiting step(s) in assembly.
Chromosomal translocations are known to be formed via non-homologous end-joining (NHEJ). Now analysis of translocations in mammalian cells lacking XRCC4/DNA ligase IV, a component of the classical NHEJ pathway, indicates that the alternative NHEJ pathway might be responsible for the majority of translocation events.
Bacterial flagellar protofilaments can adopt 2 distinct conformations (L- or R-type), resulting in different functional states (the bacteria swim or tumble). The R-type protofilament was characterized previously by cryo-EM; now the same analysis of the L-type conformation provides insight into the conformational changes involved in this switch.
High-resolution structures of p53 core domain tetramer bound to DNA containing 2 contiguous half-sites reveal a non-canonical Hoogsteen base-pairing at the center, which allows enhanced protein-DNA and protein-protein interactions. This distinct mode of recognition likely contributes to the different affinities shown by p53-regulated promoters and their different cellular outcomes.
Histone modifications have been implicated in many DNA transactions. Using a mini-chromosome isolation and mass spectroscopy technique applicable to specifically probing many DNA binding factors, the acetylation of histone residues surrounding an S. cerevisiae origin are now defined during the cell cycle, with further experiments implicating residues in efficient origin activation.
New World hemorrhagic fever arenaviruses are rodent transmitted agents that cause severe, often fatal human disease. The structure of the Machupo virus glycoprotein 1 subunit in complex with its human cellular receptor, transferrin receptor 1, was solved. The interaction interfaces between the two proteins and sequence alignments suggest that these viruses fortuitously acquired the ability to bind human transferrin receptor 1 while adapting to their natural hosts.
Covalent histone lysine modification has been linked to various DNA functions. PHF8 is a jumonji family demethylase containing a PHD domain, linked to methylated histone binding, and also to X-linked mental retardation. PHF8 is now shown to bind H3K4me3 and demethylate H3K9me1/2, a function linked here to activation of rRNA transcription.
The bacterial channel MscS opens in response to membrane tension. How exactly the the lipid bilayer and the channel gate communicate with each other is still unclear. Now molecular dynamics simulations and electrophysiology analysis of different mutants indicate the role played by contacts between lipid-facing and gate forming transmembrane helices.
Protein phosphatase specificity is usually achieved via interaction with regulatory partners, which can control their subcellular localization and/or enzymatic specificity. Now structural and functional work on spinophilin reveals its extensive interactions with PP1, which differentially restrict the phosphatase's ability to bind different substrates.
Upon recognition of a cognate, but not near-cognate, codon in the small ribosomal subunit, this information must be conveyed to the large subunit. By probing conformational changes that occur upon binding of cognate vs. near-cognate stop codons by release factor 1, signaling of this information is now examined.
The bacterial protease ClpP forms an active complex with Clp-ATPases, but can also be directly activated by a recently characterized class of antibiotics (ADEP). Now the crystal structures of Bacillus subtilis ClpP bound to ADEPs reveal the conformational changes involved in ClpP's activation.
The monoubiquitination of processivity factor PCNA at Lys164 in yeast leads to exchange of a replicative DNA polymerase with a translesion one. Now a functional, split version of monoubiquitinated PCNA is developed and its crystal structure shows that the ubiquitin moiety is located at the back face of the PCNA ring and does not cause large conformational changes in PCNA.
Myosin X is found at lamellipodia and membrane ruffles, regions with dynamic actin organization. Using single molecule analyses, the step size and properties of myosin X is now found to walk on both single and bundled filaments, step from one filament to the next on a bundle and walk helically around it.
CaiT is a membrane antiporter that catalyzes the exchange of L-carnitine with γ-butyrobetaine across the Escherichia coli membrane. The structure of CaiT indicates the existence of secondary substrate-binding sites in addition to the central primary binding site, thereby providing mechanistic insights into substrate translocation.
Capping protein (CP) regulates actin dynamics through binding to the barbed ends of actin filaments. Structural analysis of the CP interaction motifs from CARMIL and CD2AP suggests an allosteric mechanism of actin filament uncapping as a potential alternative to direct competition for actin-binding residues on CP.
The spliceosome is a complex small nuclear RNA–protein machine that removes introns from pre-mRNAs. A single-molecule fluorescence resonance emission transfer (FRET) assay using the efficiently spliced yeast pre-mRNA, Ubc4, reveals many reversible, time- and ATP-dependent changes in conformation for individual pre-mRNAs and indicates that spliceosome assembly occurs close to thermal equilibrium.
The crystal structure of the beetle Tribolium castaneum telomerase catalytic subunit (TERT) bound to a short RNA-DNA hybrid that represents the putative RNA template and the telomeric DNA is now presented, revealing the specific contacts between TERT and nucleic acid template and product.
SH2 domains are present in many proteins, and designing specific inhibitors has been a challenge. Now a monobody, based on a fibronectin type III domain scaffold, that targets the SH2 domain from Abl kinase is developed, with structural data revealing the basis of its specificity and functional work exploring its effects in vitro and in cells.