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The RITS complex links the RNAi pathway with centromeric heterochromatin formation in fission yeast and comprises the chromodomain protein Chp1, the GW protein Tas3 and the argonaute protein Ago1. X-ray analysis of the structured core of the Chp1–Tas3 subcomplex reveals the presence of a C-terminal PIN domain in Chp1, which contributes to post-transcriptional gene silencing of subtelomeric transcripts independently of RNAi.
Histone acetyltransferase Tip60 is required to activate several target genes of ERα. Now Tip60 is shown to interact directly with ERα and to recognize the enhancer marker H3K4me1, leading to transcriptional activation in response to estrogen.
NSP and Cas family proteins form multidomain signaling platforms that integrate signals to mediate cell migration and invasion. Structural analyses show that the C-terminal domain of human NSP protein BCAR3 adopts the Cdc25-homology fold of Ras GTPase exchange factors, but in a closed conformation incompatible with enzymatic activity. Instead, this closed conformation is instrumental for interactions with Cas proteins.
What happens to histones during transcription is not well understood. Atomic force microscopy snapshots of RNA polymerase II (Pol II)-nucleosome complexes before, during and after transcription show the presence of looped transcriptional intermediates. In addition, a fraction of transcribed histones are remodeled to hexasomes, and the size of this fraction depends on the elongation rate of Pol II.
The enzyme Rubisco has a central role in atmospheric CO2 fixation. Rubisco can be inactivated if its sugar substrate is bound prior to carbamylation of a residue in the active site. The structure of tobacco Rca, the enzyme that removes the bound sugar substrate and activates Rubisco, is now presented, offering insight into this process.
The mechanism by which the noncanonical E1-like enzyme Atg7 activates ubiquitin-like Atg8 to trigger autophagy has not been well understood. The crystal structures of the N-terminal domain of Atg7 alone and C-terminal domain of Atg7 in complex with Atg8 show that this probably proceeds without the need for dramatic conformational rearrangements by Atg7, distinct from other E1 enzymes.
Restoration of p53 activity is a promising chemotherapeutic approach, and because of the high binding affinity between HAUSP, MDM2 and p53, blocking HAUSP activity should have the net effect of robust p53 stabilization. HAUSP is inhibited by belt-like binding of vIRF4 from Kaposi's sarcoma–associated herpesvirus. Two peptides derived from vIRF4 can additively inhibit HAUSP, leading to p53-dependent cell cycle arrest and xenograft tumor regression.
SRP-type GTPases deviate from other GTPases in that they are not activated by GTPase-activating proteins (GAPs). New studies show that the MinD-type protein YlxH activates the SRP-GTPase FlhF, which is involved in flagellar biosynthesis. The crystal structure of the Bacillus subtilis FlhF–effector complex reveals the mechanism of activation, the general concept of which may also apply to RNA-mediated activation of the SRP-GTPases Ffh and FtsY.
The eukaryotic proteasome is composed of a regulatory particle and a core particle. Now protein cross-linking is used to map the contacts between regulatory particle and core particle subunits, revealing that some Rpt subunits engage with the core particle in a dynamic fashion that is regulated by nucleotide binding and hydrolysis.
The mitochondrial transcription factor Tfam has a role in organizing the mitochondrial genome, in addition to its transcriptional function. Structural studies of human Tfam in complex with a mitochondrial DNA promoter show that Tfam imposes a U-turn on the DNA similarly to the unrelated HU family of proteins, which play analogous architectural roles in organizing bacterial nucleoids.
The human mitochondrial transcription factor TFAM is essential for DNA packaging as well as transcription. X-ray analysis of TFAM in complex with a mitochondrial promoter reveals that TFAM induces a 180-degree bend in the DNA, which creates an optimal DNA arrangement for transcription initiation, while facilitating DNA compaction of the mitochondrial genome elsewhere.
Tubulin undergoes cycles of removal or addition of a C-terminal tyrosine residue to the C-terminus of α-tubulin within the α-β heterodimer. Crystal structures of tubulin tyrosine ligase (TTL), along with SAXS and functional analyses, reveal that TTL interacts with the C-terminal tail of α-tubulin and also with its longitudinal face, preventing incorporation of the α–β tubulin dimer into the microtubule lattice.
Dimerization, ligand-binding and co-confinement are all expected to contribute to erbB1 signaling, but the level of their contribution has not yet been fully appreciated. Two-color quantum-dot tracking in live cells now shows that ligand-binding (two ligands with two receptors) stabilizes erbB1 dimers, whereas actin networks influence dimer mobility and promote repeated encounters between erbB1 monomers.
TiaS catalyzes the transfer of agmatine onto the first position cytidine of the tRNAIle2 anticodon in archaea, ensuring proper translation of the matching codon. Now the crystal structures of the TiaS–tRNAIle2 complex with ATP, or with AMPCPP and agmatine, reveal a novel kinase domain and show how TiaS selects the correct tRNA while segregating the target cytidine until agmatine is bound.
Monoclonal antibody 2F5 recognizes the membrane proximal external region (MPER) in GP41 and has broad neutralization activity against HIV-1 strains. NMR, EPR and HDX/MS analyses now show that 2F5 extracts MPER from the membrane using a scoop-like movement.
Archaea use a tRNAIle with agmatine conjugated at the C34 position to decode the AUA codon. The enzyme that catalyzes this reaction, TiaS, has been previously identified, and it is now shown that it uses a novel kinase domain to hydrolyze ATP into AMP and pyrophosphate before phosphorylating itself and the tRNA on its way to conjugating the agmatine.
Eukaryotic initiation factor eIF2 binds initiator Met-tRNAiMet to the P site of the 40S ribosomal subunit. Hydroxyl radical probing analyses allowed mapping of the binding of eIF2 on the ribosome and on Met-tRNAiMet. Interestingly, despite having structural similarities to elongation factor EF-Tu, which delivers aminoacyl-tRNAs to the A site of 70S elongating ribosomes, eIF2 binds tRNA in a substantially different manner.
Organism-wide RNA interference (RNAi) is due to the movement of mobile RNA species throughout the organism. New genetic evidence shows that double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNAs in Caenorhabditis elegans. Interestingly, single-stranded primary and amplified secondary siRNAs do not generate mobile silencing RNAs.
NuA4 is an essential and conserved histone acetyltransferase (HAT) complex. Using electron microscopy supported by biochemical analyses, insights are now gained into its interaction with the nucleosome core particle (NCP). These data indicate that the Epl1 subunit is essential for NCP interaction, whereas the Yng2 subunit positions the acetyltransferase complex relative to specific histone tails.
Deficiencies in aprataxin, which reverses 5′-adenylate DNA adducts, can lead to the neurodegenerative disorder AOA1. Mutagenesis analyses and the crystal structure of the aprataxin ortholog from Schizosaccharomyces pombe in complex with DNA, AMP and Zn2+ reveal the mechanisms by which this enzyme processes DNA lesions and maintains genome integrity.
