News & Views in 2008

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  • New work shows that a toxin that normally kills the yeast Saccharomyces cerevisiae by cleavage of tRNA substrates can be neutralized by RNA ligases that repair the damage, suggesting that these ligases may have a more general role in tRNA repair in the cell.

    • Eric M Phizicky
    News & Views
  • Crystal structures of the Nipah and Hendra virus attachment protein complexed with ephrin-B2 shed light on the apparent paradox of ephrin-B2's flexibility for binding multiple receptors. Surprisingly, the switch from the use of glycan-based to protein-based receptors seems to have evolved independently from other protein-receptor–using paramyxoviruses such as the measles virus.

    • Benhur Lee
    • Zeynep Akyol Ataman
    • Lei Jin
    News & Views
  • New work shows that activation of the Ras guanine nucleotide exchange factor SOS is dependent upon the membrane density of phosphatidylinositol-4,5-bisphosphate (PIP2) and GTP-bound Ras. These signals synergize to release the autoinhibitory DH-PH domain, while the histone domain fine-tunes SOS activation in response to PIP2.

    • Greg M Findlay
    • Tony Pawson
    News & Views
  • Methylated lysines are essential components of the network of histone modifications, or 'histone code', that regulates gene expression. Work on the methyltransferase Dot1 shows how modifications on different histones interact to modulate activity and how its catalytic mechanism is matched to its role in genome regulation.

    • Bryan M Turner
    News & Views
  • Small molecules that safely antagonize amyloidogenesis are desperately needed for many devastating disorders that plague humankind, including Alzheimer's and Parkinson's diseases. New work brings important mechanistic insights into how one promising candidate, (−)-epigallocatechin-3-gallate (EGCG), diverts amyloid-β and α-synuclein down innocuous folding trajectories at the expense of the deleterious states populated during amyloidogenesis.

    • Blake E Roberts
    • James Shorter
    News & Views
  • Organisms possessing RNA-dependent RNA polymerase activity are known to produce endogenous small interfering RNAs (esiRNAs). It had been thought that organisms such as flies and mammals lacking this activity would not produce esiRNAs. However, it has now been shown that a functional esiRNA pathway is present in such animals; the esiRNAs are derived from a variety of endogenous double-stranded RNA substrates.

    • Timothy W Nilsen
    News & Views
  • The splicing pathway is dominated by ATP-dependent RNA rearrangements promoted by DEAD-box helicases. Post-translational modifications have now been implicated in the regulation of two DEAD-box proteins that are required for catalytic activation of the spliceosome.

    • Corina Maeder
    • Christine Guthrie
    News & Views
  • Chromosomal breaks destabilize the genome and can cause developmental defects and diseases such as cancer. New work suggests that, shortly after DNA damage, dissociation of the histone binding protein HP1β from chromatin facilitates restoration of genome integrity.

    • Jiri Lukas
    • Jiri Bartek
    News & Views
  • A heterotrimeric complex of minor pseudopilins from the type II secretion system has been identified and its crystal structure solved. Although each subunit shares the same overall α-β fold as other characterized (pseudo)pilins, GspK has a unique large α-helical domain inserted between two canonical β-strands. The structure constrains models for pseudopilus assembly.

    • Katrina T Forest
    News & Views
  • Since the discovery that actin and actin-related proteins (ARPs) reside in the nucleus as integral subunits of chromatin-modifying and chromatin-remodeling complexes, efforts to uncover their roles in chromatin regulation have met with limited success. In a new study, the previously mysterious helicase-SANT–associated (HSA) domain found in many chromatin regulatory complexes is shown to act as a module that directs recruitment and contributes to the action of actin and ARPs in chromatin regulation.

    • Aaron J Gottschalk
    • Ronald C Conaway
    • Joan Weliky Conaway
    News & Views
    • Sabbi Lall
    News & Views
  • The INO80 chromatin-remodeling complex has roles in transcription, DNA repair and replication. By studying the role of Ino80 in DNA replication, a study now finds that the INO80 complex is essential for replication fork progression under conditions of replicative stress, stabilizes stalled forks and helps ensure proper restart.

    • Kelly M Trujillo
    • Mary Ann Osley
    News & Views
  • Two proposed mechanisms for how microRNAs (miRNAs) and their associated Argonaute proteins inhibit translation in mammals do not seem to operate in Drosophila melanogaster cells, suggesting that insights into important miRNA functions remain elusive. However, the interaction between Argonaute and the P-body factor GW182 may help in elucidating the biochemical basis of translational control by miRNAs.

    • Joel D Richter
    News & Views
  • The ankyrin repeats of the G9a and GLP histone methyltransferases have now been shown to be binding modules for mono- and dimethyllysine histone H3 lysine 9 (H3K9), revealing a new function for an ankyrin repeat domain and showing that a polypeptide chain can both create and recognize the same histone mark.

    • Michael M Brent
    • Ronen Marmorstein
    News & Views
  • Assembly of the 34-subunit, 2.5 megadalton 26S proteasome starts with formation of the seven-membered α-ring. A set of newly identified proteasome chaperones serves as a clamp to seal α-rings with the correct composition. By regulating the efficiency and outcome of this crucial step in proteasome biogenesis, these dedicated proteasome chaperones apparently partake in the stress response and in adaptation to intracellular proteolysis needs.

    • Rina Rosenzweig
    • Michael H Glickman
    News & Views
  • The compositional complexity of the spliceosome creates a serious obstacle for its experimental analysis. Purification of a compositionally defined splicing complex C capable of completing the second step of splicing in the absence of additional proteins opens the door for future mechanistic and structural analyses.

    • Maria M Konarska
    News & Views
  • The kinase regulatory-loop binding (KRLB) region of insulin receptor substrate 2 was originally thought to be a new type of domain with binding properties similar to phosphotyrosine binding (PTB) domains. A crystallographic study now shows that KRLB is actually a short peptide segment that binds to the insulin receptor using an extended series of contacts that mimic both autoinhibitory loop and ATP binding to its catalytic cleft.

    • Sang Youn Park
    • Steven E Shoelson
    News & Views
  • An immense range of polysaccharide structures is expressed on the bacterial surface. The length of the polymer can be a crucial attribute for virulence. Members of a family of 'polysaccharide copolymerase' proteins are essential for the regulation of polymer chain length, participating in one widespread biosynthesis scheme.

    • Chris Whitfield
    • Kane Larue
    News & Views