Research articles

APOBEC3G is a cytidine deaminase that can be incorporated into HIV-1 virions and process the viral genome upon cell infection, leading to viral hypermutation and inactivation. APOBEC3G's activities are counteracted by viral protein Vif. Using a sensitive enzymatic assay, low levels of APOBEC3G can be detected associated to Vif(+) virions. Furthermore, the authors show that APOBEC3G functions in a distributive manner and causes dispersed hypermutation via intersegmental transfer.

Kinesins are molecular motors that slide along microtubules. A quantum dot is now attached to a microtubule, allowing the visualization of its rotation as it is moved by kinesins. The rotational pitch provides information about the motor, revealing the low processivity of human mitotic kinesin Eg5.

The binding of kinesin to microtubules promotes nucleotide exchange by the kinesin. Structural studies of the intermediate states of nucleotide exchange reveal the sequence of interactions and conformational changes that occur and the role of Mg²⁺ in the process, providing a testable model for microtubule-activated ADP release.

Glycine receptors (GlyR), part of the Cys-loop neurotransmitter receptor family, are Zn²⁺-modulated ion channels. Electrophysiological studies on GlyR mutants indicate that the hydrophobic cores of the channel's ligand binding domains are important for allosteric communication between the ligand-binding and Zn²⁺-inhibitory sites. The findings suggest a general activation mechanism for this receptor family.

S-adenosyl-L-methionine is a methyl donor in many biological reactions and in bacteria regulates gene expression through binding to the SAM riboswitch. The structure of a third class of SAM riboswitches now indicates which features of SAM the riboswitches have converged on to distinguish it from the closely related S-adenosyl-L-homocysteine.

Histone methylation has important consequences for chromatin activity. Now, histones with methyllysine analogs are used to reconstitute nucleosomes: the crystal structures show no global changes in nucleosomes with H3K79me2 and H4K20me3, but the latter modification enhances compaction of nucleosomal arrays.

In vitro, pure tubulin assembles into B-lattice microtubules, in which lateral αα and ββ contacts between tubulin heterodimers predominate. Mal3, a homolog of the plus end–tracking protein EB1, is now shown to promote microtubule assembly into an A-lattice arrangement, forcing reconsideration of in vivo microtubule structure.

Substitution of the active site gatekeeper residue in the BCR-ABL oncoprotein and related kinases is a common mechanism of imanitib resistance but has also been observed in drug-naïve patients. New work suggests that this residue stabilizes a hydrophobic spine that links the N and C kinase lobes, promoting the active conformation, and that adverse mutations at the gatekeeper residue further stabilize the spine. Disruption of the spine would be an attractive new goal in drug development.

Rad51 is an essential protein with a central role in homologous recombination. An N-end rule degron Rad51 is now used in DT-40 cells to show that Rad51 is not required for DNA synthesis, but it is necessary to resolve RPA-bound DNA structures during G2.

SRp38, unlike other SR proteins, functions as a general splicing repressor when it is dephosphorylated. When phosphorylated it functions as a sequence-specific splicing activator and also affects the selection of mutually exclusive exons in the GluR-B pre-mRNA. Thus, SRp38 is a previously uncharacterized kind of splicing factor that can switch from a repressor to an activator and regulator of alternative splicing.

Viral fusion proteins are required for the fusion of viral and host membranes for all enveloped viruses. The structure of the Baculovirus postfusion form of glycoprotein gp64, a class III fusion protein, explains its ability to fuse with many different cell types, and structural comparisons suggest that all three classes of fusion proteins may be more closely related than previously thought.

Caspases are cysteine proteases that have a central role in triggering apoptosis; thus, it is essential to tightly control their activity. Now a caspase inhibitor has been identified in Caenorhabditis elegans: CSP-3 is a caspase homolog that associates with the CED-3 zymogen, inhibiting its autoactivation.

Mutation of Cid14, a key enzyme in the TRAMP RNA surveillance pathway, has previously been shown to decrease small interfering RNA production in Schizosaccharomyces pombe. Analysis of Argonaute-associated proteins now indicates that, in the absence of Cid14, RNAs usually processed by TRAMP now enter the small interfering RNA pathway, suggesting that the RNA surveillance pathway prevents abundant RNAs from entering the RNA interference pathway.

Certain bacterial enzymes are packaged within protein chambers that provide a confined environment for their reactions to take place. Ban and colleagues now identify a family of proteins that form nanocompartments, similar to bacterial microcompartments such as the carboxysome, and show that the enzymes within are anchored by their C-terminal extensions to binding sites on the inner surface of the chamber.

MicroRNAs are processed by Drosha, and previous data had suggested that this occurred soon after transcription. Following Drosha recruitment and using nuclear run-on technology, data now indicate that miRNAs both within and outside of introns are processed co-transcriptionally and that exonucleases enter the fray to aid processing before splicing, implying that Drosha cleavage influences the maturation of the pre-mRNAs in which miRNAs reside.

Formation of β-2 microglobulin (β2m) amyloid fibrils is associated with dialysis-related amyloidosis. β2m pre-amyloid formation occurs in a Cu²⁺-dependent manner in vitro. Structural studies reveal that structural changes away from the Cu²⁺ binding site create conditions that promote β2m oligomerization leading to amyloidogenesis.

The Est3 telomerase subunit has a critical, but still uncharacterized regulatory role in yeast telomere maintenance. An OB-fold is now predicted for Candida albicans Est3 protein, and residues important for its association with the telomerase complex are identified.

The Est3 telomerase subunit has a critical, but still uncharacterized regulatory role in yeast telomere maintenance. An OB-fold is now predicted for Saccharomyces cerevisiae Est3 protein, and residues important for its association with the telomerase complex are identified.

In pregnancy-associated malaria, parasite-infected erythrocytes express the protein VAR2CSA on their surface and bind to chondroitin sulfate A in the placenta, with severe effects to the mother and the fetus. Now the crystal structure of a domain of VAR2CSA in complex with chondroitin sulfate A is reported and, together with functional studies, sheds insight into this interaction.

Group A trichothiodystrophy is caused by mutations in the p8 subunit of the TFIIH complex, involved in transcription and nucleotide-excision repair. Now the structure of the yeast ortholog of p8 in complex with a fragment of the yeast ortholog of p52 shows how p8 stabilizes p52 and thus the whole TFIIH complex.