Brief Communications

The structure of Moxifloxacin, a quinolone antibacterial, in complex with Acinetobacter baumannii topoisomerase IV and DNA now shows how the drug stacks between base pairs at the DNA cleavage site. Moxifloxacin contacts the protein through a non-catalytic Mg²⁺, and the structure gives insight into the mode of inhibition and possible basis of drug resistance.

BRCA2 is a tumor suppressor that interacts with RAD51 and functions in homologous recombination, but understanding its precise functions has been hampered by difficulties in purifying such a large protein. Now purified full-length human BRCA2 is shown to bind ∼6 molecules of RAD51 and to promote RAD51 binding to RPA-covered ssDNA in a manner stimulated by DSS1.

Tumor suppressor protein BRCA2 interacts with RAD51 and functions in homologous recombination, but understanding its precise functions has been hampered by difficulties in purifying such a large protein. Now purified full-length human BRCA2 is shown to bind selectively to ssDNA, to promote RAD51 binding to ssDNA while reducing its association with dsDNA, and to stimulate RAD51-mediated DNA strand exchange.

The MSL complex is conserved and in Drosophila melanogaster is involved in spreading of gene activation on the male X chromosome. Structural and functional analyses of the MSL3 chromodomain now indicate that DNA binding promotes methylated histone tail binding, suggesting coordinated binding that is here proposed to promote cross-nucleosome interaction in an array.

Previously, the molecular chaperone Hsp90 has been shown to copurify with RISC (RNA-induced silencing complex), involved in small RNA-mediated silencing. It is now shown that Hsp90 is needed for AGO2 to be loaded with a siRNA duplex by the RISC-loading complex suggesting a model where it is involved in modifying AGO2 conformation.

mTERF is a mitochondrial protein involved in transcription and replication pausing. The crystal structure of human mTERF bound to DNA now reveals the presence of nine repeats that form a left-handed solenoid, named the Zurdo domain.

The crystal structure of human DNA pol beta with DNA template and an incoming 8-oxo-dGTP forming a mutagenic pair with template base A is now presented, revealing the structural constraints within the polymerase active site that result in this mutagenic incorporation.

The PWWP domain has been identified in a number of nuclear proteins that interact with histones including BRPF1. Structural and functional analysis of this domain from BRPF1 now argue that it specifically recognizes methylated histone H3 Lys36, identifying this widely conserved domain as a reader of this mark.

Many actin-binding proteins contain calponin homology (CH) domains, but the manner in which these domains interact with F-actin has been controversial. Electron microscopy analyses show that the tandem CH domains of α-actinin bind to F-actin in an open conformation and that opening of these domains might be a key regulatory mechanism for proteins with tandem CH domains.

Nonsense-mediated mRNA decay (NMD) recognizes and degrades mRNAs with premature termination codons. In yeast, this occurs by decapping followed by 5' to 3' exonucleolytic digestion. New work shows that substrates of NMD pathway are targeted for decapping while the mRNA is associated with polyribosomes. These findings are in contrast to previous work which suggested that NMD occurs in ribosome-free P bodies but are consistent with recent work showing that 'normal' mRNAs are decapped co-translationally.

The solution structures of the two PAR-binding zinc finger (PBZ) modules from APLF, a human protein putatively involved in DNA damage response, are now presented. Together with binding studies with PAR fragments and mutagenesis, the work sheds light on PAR recognition by PBZ modules.

Respiratory syncytial virus (RSV) is a highly contagious illness in young children. The structure of antibody drug motavizumab in complex with a 24-residue peptide corresponding to its epitope on RSV-fusion glycoprotein suggests why it is more potent than its predecessor, palivizumab (Synagis).

GW182 has been implicated in the effector steps of microRNA-mediated repression and recently shown to interact with the Poly(A) binding protein C-terminal domain (PABPC1). The structure of PABPC1 in complex with a human GW182 paralog peptide, now gives insight into the interactions needed to elicit target deadenylation.

Helicobacter pylori is a strong risk factor for stomach cancer. The CagA effector protein is translocated into host cells by a type IV secretion system and is a key virulence factor. Its effects are mediated in part through the host polarity kinase PAR1b/MARK2, which CagA binds and inhibits. The crystal structure of a complex between CagA peptide and MARK2 reveals that the CagA peptide mimics targets of this kinase family.

The TAK1 kinase binds K63-linked ubiquitin specifically via its TAB2 subunit. The structure of the TAB2 NZF domain in complex with K63-linked ubiquitins now indicates that this domain interacts with neighboring ubiquitins through distinct sites, explaining the basis of specific recognition.

De novo methylation of DNA can affect the function of underlying genes and transposons in plants. Using a genetic screen, two factors required for de novo demethylation in Arabidopsis thaliana are identified and analyzed.

Phage lysis requires the enzymatic degradation of the host cell wall by a phage-encoded lysin. Secretory endolysins are inactive at the membrane but active in the cytoplasm, and the signal-anchor-release (SAR) domain is shown to be essential for regulating its effects. The structure of coliphage 21 lysozyme explains how this endolysin is controlled.

The poxvirus 2L protein binds tumor necrosis factor-α (TNFα). Structural data now indicate that 2L interacts with TNFα at a site overlapping with that for its receptor, arguing for the basis of inhibition of receptor interaction and TNFα-induced immune responses.

Sialic acid is the most abundant terminal monosaccharide on mammalian cell surface glycoconjugates. The crystal structures of a mammalian sialyltransferase, that of porcine ST3Gal-I, in the apo form and bound to analogues of the donor and acceptor substrate are now described, providing insights into the catalytic mechanism and for inhibitor design.

The anaphase promoting complex (APC) is a key cell-cycle regulator that has ubiquitin-ligase activity. The first structure of a complex formed between APC subunits, that of CDC26 and APC6, provides detailed structural information of APC components and suggests how CDC26 may stabilize APC6 and other complex subunits.