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NTPases use a metal ion, typically Mg2+, coordinated by a conserved serine or threonine residue, to enable phosphate binding and catalysis. Now cysteine substitutions at the switch 1 motif of different kinesins render them able to use Mn2+ instead of Mg2+, allowing their enzymatic and motor activities to be modulated by the ratio of Mg2+ to Mn2+.
Cis-encoded antisense RNAs (asRNAs) are transcribed from the DNA strand opposite another gene and function by pairing with RNAs expressed from the complementary strand. A new study provides evidence that a bacterial cis-asRNA acts in trans, using a domain outside of its target complementarity sequence, suggesting the need for a mechanistic re-evaluation of asRNA-based gene regulation.
The type III ribonuclease DCR-1 is essential for ERI endogenous RNAi and exogenous RNAi in Caenorhabditis elegans. A new study shows that DCR-1 forms exclusive complexes in each pathway, and characterization of the ERI complex implicates a tudor domain protein in tethering an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi.
The Msn2 transcription factor is translocated to the nucleus to activate transcription of hundreds of genes in response to various environmental stimuli. Experimental and computational single-molecule analyses reveal how different stimuli elicit different dynamical patterns of Msn2 translocation, which are interpreted by promoters with distinct properties to produce specific patterns of target gene expression.
Eukaryotic MutSβ is a heterodimer composed of Msh2 and Msh3 that recognizes insertion-deletion loops (IDLs) and 3′ overhangs during mismatch repair. Now crystal structures of MutSβ in complex with DNA, containing IDLs of varying lengths, reveal that this complex interacts with its substrate differently than MutSα and bacterial MutS do.
Genome-wide association studies have established a link between the extracellular chaperone clusterin and susceptibility to Alzheimer's disease. A fluorescence approach is now used to reveal that clusterin sequesters Aβ1–40 oligomers and prevents them from undergoing further aggregation.
Recent work has indicated that the Escherichia coli replisome contains three DNA polymerases that are used to replicate two parental strands. A single-molecule approach is now used to compare replisomes reconstituted with two or three polymerases, revealing that the presence of a third polymerase ensures higher processivity overall and more efficient replication of the lagging strand.
The OTU domain deubiquitinase TRABID specifically hydrolyzes atypical Lys29- and Lys33-linked diubiquitin chains. Structural analysis of TRABID reveals an unpredicted ankyrin-repeat domain that binds ubiquitin and is crucial for TRABID efficiency and linkage specificity in vitro and in vivo.
Rab small G proteins regulate membrane trafficking events by recruiting effectors that mediate vesicle tethering. In vitro studies now suggest that Vps21 and other endosomal Rabs in budding yeast can undergo GTP-regulated Rab-Rab interactions that drive tethering in the absence of effectors, implying that they have an intrinsic tethering activity that may function in concert with conventional effectors.
Lin28 prevents the processing of pre-let-7 RNAs, but it is not clear where the Lin28 RNA binding domains interact with the RNA. The NMR structure of the Lin28 zinc knuckles with a short RNA motif reveals that each knuckle interacts with an AG dinucleotide, allowing the determination of a consensus motif for pre-let-7 recognition.
The combination of an F-box domain with a single-domain antibody that recognizes green fluorescent protein (GFP) now allows controlled depletion of GFP fusions in mammalian cells and in flies. This system, called deGradFP, should be widely useful, as GFP fusions are available for many proteins in model organisms.
Every issue of NSMB is special to us, but this one marks the end of 2011 with two features that deserve extra attention: a Commentary and an Essay Collection. These pieces and the research articles presented in this issue illustrate what NSMB is all about.
Until recently, few potent and broadly neutralizing HIV-specific antibodies had been identified, but recent findings have inspired optimism that an effective HIV vaccine can finally be developed. Here we review these studies, which used state-of-the-art high-throughput techniques to collectively describe hundreds of new potent and broad HIV-neutralizing antibodies isolated from HIV-infected individuals.
The editors of Nature Structural & Molecular Biology have assembled a special Essay Collection, coinciding with the 40th anniversary of the Protein Data Bank, to reflect on the history and future of structural biology. These personal accounts collectively tell the history of structural biology and provide perspectives on the direction of the field and challenges that it faces.
The histone variant H2A.Bbd inhibits folding of nucleosomal arrays and reverses chromatin-mediated transcriptional repression in vitro. New studies have uncovered the related mouse H2A variant H2A.Lap1 as a novel component of the transcription start site of active genes during specific stages of spermatogenesis, which enables transcriptional activation by unfolding the chromatin locally.
A system to reconstitute a collapsed replication fork using Xenopus laevis egg extracts is developed. The study shows that upon fork collapse, DNA Pol epsilon and the GINS complex are uncoupled from the replisome, and their reloading onto DNA requires repair proteins Rad51 and Mre11.
