Articles in 2009

Mek1 and Mek2 are kinases that phosphorylate Erk, participating in the signal transduction pathway controlling cellular growth and adhesion. Though closely related, there are clear functional differences, with Mek1 being subject to negative-feedback regulation via phosphorylation by Erk. Now Mek1 and Mek2 are shown to form a heterodimer in vivo, in which Mek2 activity is also controlled by Erk phosphorylation of Mek1.

The DEAD-box protein DBP5 is involved in yeast mRNA export, though the mechanism by which it helps to remodel and release transcripts on the cytoplasmic face of the nuclear pore complex has been unclear. The structures of DBP5 in complex with the mRNA and AMPPNP, as well as with the nucleoporin NUP214, indicate that the transcript and nucleoporin compete for the same binding site, suggesting a model for the sequence of events occurring at the last step of export.

Photosystem II (PSII) catalyzes the first light-dependent step in photosynthesis. An improved structural model of a cyanobacterial PSII provides complete assignment of all subunits in the complex and reveals possible channels used for the transport of protons, oxygen and water to the thylakoid lumen.

KSRP is involved in mRNA instability, a role that is repressed upon AKT kinase–mediated phosphorylation, which promotes 14-3-3 interaction. This modification site is now shown to be exposed upon AKT phosphorylation through unfolding of the KH1 domain of KSRP, an event that allows 14-3-3 interaction, which in turn affects nuclear cytoplasmic partitioning.

The ATPase and the microtubule binding domains of dynein are separated by a long stalk coiled coil, which has to communicate and coordinate the activities of these domains along the mechanochemical cycle. Now this communication is shown to occur via sliding of the α-helices of the coiled coil.

Rare codons along transcripts have been proposed to influence the local rate of translation and the folding of nascent polypeptide chains. Now this idea is demonstrated for a bacterial protein: rare-codon clusters are shown to affect translation rates, and this was important for efficient protein folding in vitro and in vivo.

Meiosis is a highly conserved and tightly regulated process in which one round of DNA synthesis is followed by two rounds of division. By studying the expression of crs1 pre-mRNA, a meiotic cyclin in fission yeast, Wise and co-workers found that increased RNA accumulation during meiosis is not due to an increase in transcription but rather is a result of RNA processing and turnover. Moreover, they found that polyadenylation of crs1 is linked to splicing, a coupling previously thought to occur only in mammals. They suggest that this highly integrated crs1 regulatory system may allow a rapid response to adverse conditions.

Now that we are well into 2009, I can't help but think about the year that has passed. Fear not, this will not be one of those dreaded holiday letters where we list all the highs and lows of the year. But as I look back, there are many things I hope that I have permanently crossed off my 'To Do' list and others that I am looking forward to doing.

Large, multisubunit complexes have been implicated in tethering transport vesicles to organelle membranes before membrane fusion. New structures add to the growing list of tethering complexes that contain conserved helical bundle structures and provide a first glimpse of how these complexes are assembled.

The DNA-repair machinery is faced with the significant challenge of differentiating DNA lesions from unmodified DNA. Two recent publications, one in this issue of Nature Structural & Molecular Biology, uncover a new way of recognizing minimally distorting DNA lesions: insertion of a 3- or 4-amino-acid wedge into DNA to extrude the lesion into a shallow binding pocket that can accommodate various damaged bases.

MukBEF, the bacterial prototype of eukaryotic condensins and cohesins, has a key role in the global chromosomal organization of Escherichia coli and its close relatives. The recent report of the crystal structure of the MukB head domain in complex with its accessory subunits MukEF clearly demonstrates that MukBEF functions as a macromolecular assembly rather than a set of individual molecules and offers clues on how ATP and MukEF regulate the architecture of this complex.

Nucleosomes can be closely spaced in vivo, suggesting that they may on occasion approach one another or even meet. Using in vitro dinucleosomal model systems, positioned nucleosomes, as well as nucleosomes in the process of being repositioned, are now shown to overlap, forming single, compact particles, with one histone dimer ejected in the process. The potential relevance to remodeling processes is discussed.

Endonuclease V can initiate the repair of deaminated purine bases by recognizing them and hydrolyzing the second phosphodiester bond on their 3′ side. Now the crystal structures of endonuclease V in complex with its substrate and its product reveal a wedge motif acting as a minor groove–damage sensor and a pocket to recognize the lesion; the enzyme remains tightly bound to the 5′ phosphate product, perhaps to hand it over to downstream repair factors.

MIA40, found in the mitochondrial intermembrane space, is a central component in the import system that transports certain cysteine motif–containing proteins into the mitochondria. New analyses reveal that MIA40 forms a novel thioredoxin fold. Its redox center catalyzes the formation of the first disulfide bond of a substrate, causing the susbtrate's second disulfide to require only oxygen for its formation.

MicroRNA target sites tend to reside in the 3′ untranslated regions of transcripts in animals. By altering the stop codon position in a model target and thus placing miRNA target sites within open reading frames, it is now found that translation through a miRNA target region is refractory to miRNA-mediated repression.

Activation of the 20S proteasome requires the binding of regulatory proteins such as the 19S regulatory particle, which opens the 20S gates allowing substrate access to the active sites. New data now indicate that binding of a polyubiquitylated substrate to the 19S particle allows further opening of the 20S gates, suggesting a feedforward mechanism for 20S activation.

One of the key early steps in splicing is recognition of the 5′ splice site by base-pairing to the U1 small nuclear RNA. Data now indicate that U1 can shift to recognize what had been designated as atypical 5′ splice sites, broadening the scope of what can be recognized as a functional splice site by the canonical machinery and thus impacting both splicing predictions and mechanism, as well as providing a potential mechanism underlying a puzzling mutation associated with pontocerebellar hypoplasia.

RDE-1 is a Caenorhabditis elegans Argonaute homolog involved in mediating the primary response to small RNA interference. Analyses now indicate that the RNase H–homologous region of RDE-1 is not needed for target cleavage, but is specifically required for removing the passenger strand of fully complementary siRNA duplexes.