News & Views in 2009

Previous structural snapshots of snurportin have provided insights into its cargo recognition and nuclear import. The structure of snurportin bound to its export factor CRM1 now reveals the molecular basis of its recycling back into the cytoplasm, illuminating general principles of nuclear export sequence recognition.

Type III secretions systems (T3SSs) are major bacterial virulence factors responsible for secretion and injection of protein effectors into host cells. New structures illuminate their ring structure and identify novel ring-mediating structural scaffolds.

Development and maintenance of an organism require the precise spatiotemporal orchestration of stem cell proliferation and differentiation. In neurogenesis, a microRNA and an orphan nuclear receptor comprise a negative feedback loop that regulates neural stem cell fate.

Many cellular fates are determined by different genetic programs, but the regulation of cellular differentiation is still not well understood. Besides the possible control exerted by the activity and combination of transcription factors, there are multiple RNA processing mechanisms, ensuring differential gene expression.

Two papers present strong evidence that the codon-anticodon interaction is poised on a tipping point so that, given a nudge, the tRNA can insert the wrong amino acid into the growing polypeptide chain, leading to translational fidelity loss.

Intermediate conformations of the Hsp90 ATPase cycle have been identified in solution by fluorescence resonance energy transfer, and the impact of nucleotides and of modulatory cochaperones has been visualized in real time.

The influenza virus has proved an elusive target in the development of broadly protective vaccines. A new study identifies an antibody with broad neutralizing activity against influenza viruses of different subtypes. The antibody recognizes a highly conserved region on the viral hemagglutinin that may be targeted to prevent infection.

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.

Biochemical studies on the spliceosomal helicase Brr2 reveal that it is activated by Prp8, the master regulator of the splicing cycle. Substitutions in Prp8 that cause retinal degeneration in humans block activation of Brr2, providing insight into the molecular pathology of retinitis pigmentosa.

Endonucleases have generally not been considered among the major factors in well-studied mRNA-decay and quality-control pathways in mammals and yeast. However, two important players in these pathways, the exosome and SMG6, have now been shown to contain functionally significant endonucleolytic activities.

The formation of heterochromatin involves spreading of repressor proteins along large chromosomal domains. A new study reveals that the concept of spreading also holds true for establishing domains of active chromatin. More specifically, spreading of the Drosophila melanogaster male-specific lethal (MSL) activator complex, which is required for dosage compensation on the X chromosome, involves interaction between the MSL3 chromodomain and histone H3 methylated at lysine 36.

Alternative splicing is typically thought to be controlled by RNA binding proteins that modulate the activity of the spliceosome. A new study not only demonstrates that alternative splicing can be regulated without the involvement of auxiliary splicing factors, but also provides mechanistic insight into how this can occur.