Reviews & Analysis

How can a single protein recognize and bind a variety of partner proteins that vary in sequence and structure? Analysis of the nuclear export receptor CRM1 provides new insight and surprising conclusions.

The interaction of the Fas death domain (DD) with the adaptor protein FADD is a critical step in assembling the death-inducing signaling complex (DISC). Using structural and biophysical approaches, two recent papers reveal the core stoichiometry to be a 5Fas:5FADD complex.

The N-end rule pathway is a proteolytic system in which recognition components (N-recognins) recognize a set of N-terminal residues as part of degradation signals (N-degrons). Two studies in this issue report the structures of Ubr boxes, a substrate recognition domain of eukaryotic N-recognins. We discuss how eukaryotic and prokaryotic N-recognins use a similar molecular principle to recognize a different set of N-degrons.

In this issue, Wu et al. show that the RecBC helicase, which is involved in repairing double-strand DNA breaks, uses one ATPase motor to drive two translocases along opposite strands of DNA—much as an all-wheel drive engine controls movement of both front and back wheels. This mechanism may allow RecBC to load onto blunt-end DNA more efficiently and to move through obstacles such as gaps and DNA damage.

The HIV-1 Tat protein promotes viral transcription elongation by recruiting P-TEFb to RNA element TAR on the viral mRNA. Recent work from D'Orso and Frankel uncovers unexpected aspects of this process.

A detailed quantitative model of signaling by IRE1 sheds light on the mechanism of its activation by endoplasmic reticulum stress and addresses a long-standing controversy in the field.

To cope with the life-threatening crisis of a DNA interstrand cross-link (ICL), human cells must invoke the Fanconi anemia (FA) DNA repair pathway. The FA pathway is a multistep repair process, requiring multiple nucleolytic incisions and translesion DNA synthesis. Recent work from four laboratories has identified a novel FA-associated nuclease, FAN1, that binds directly to monoubiquitinated FANCD2, resolving a decade-long puzzle regarding the function of this FANCD2 modification.

The signal recognition particle (SRP) has evolved in chloroplasts to include new components, new ways of recognizing targeting substrates and new capabilities that prevent aggregation of protein-targeting substrates or even rescue substrates from an aggregated conformation. Unique attributes of chloroplast SRP are focused toward localizing a single family of nuclear-encoded chlorophyll-binding proteins to thylakoid membranes and suggest that the successful migration of this gene family to the nucleus was tied to evolutionary adaptations in chloroplast SRP.

In this issue, Ishikawa and colleagues provide direct evidence to support the 'winch' hypothesis for the dynein motor mechanism, in which the AAA domain motor unit is displaced parallel to the doublet microtubule long axis rather than undergoing a rotary motion.

Stringent post-transcriptional regulation of the amyloid precursor protein (APP) is critical for maintaining proper neurological function. In this issue, Lee et al. identify two RNA-binding proteins, FMRP and hnRNP C, that have opposite effects on APP translation via competing interactions, surprisingly, with the mRNA coding region.

Crystal structures of a calcium-dependent protein kinase from Toxoplasma gondii uncover a unique mechanism of activation and potential avenues for selective inhibition.

In this issue, three papers report the distribution of the RNA polymerase III (Pol III) machinery, including transcription factor IIIB, transcription factor IIIC and Pol III itself, across the human genome. These studies reveal cell type–specific expression of Pol III genes, functional interplay between the Pol II and Pol III transcriptional machineries and the potential involvement of Pol III genes in chromosome organization.

A new crystal structure of an anti–HIV-1 envelope antibody bound to an envelope–receptor complex shows the antibody binding both the HIV-1 envelope and the CD4 receptor, raising the question of what the role of antibody autoreactivity in host responses to HIV-1 may be.

The tumor suppressor p53 protects the cell from cellular stress, and in so doing it decides between cell-cycle arrest and cell death. The high-resolution structure of four DNA binding domains of p53 in complex with DNA shows how the structural collaboration between protein and DNA may influence the biological outcomes of the tumor suppressor.

Eukaryotic cells have numerous non–membrane bound bodies whose functions are often unclear. On page 403 of this issue, Strzelecka and colleagues provide evidence that the ability to form Cajal bodies increases the rate of small nuclear ribonucleoprotein (snRNP) biogenesis and/or function. This supports the hypothesis that some cellular bodies form to increase the rates of assembly of multicomponent cellular machines.

Two recent papers break major new ground on the issues of NHEJ, backup pathways for NHEJ and how these relate to the chromosomal translocation process.

In this issue, a long-awaited report sheds new light on the strange performance of bacterial flagellar filaments. We now have high-resolution data on two different, 'switched' versions of the structure.

Synaptotagmins and SNAREs are known to couple Ca²⁺ sensing to membrane fusion during Ca²⁺-triggered exocytosis, but unraveling the mechanism of this coupling has proven extremely difficult. Two studies in this issue now provide crucial insights into the nature of synaptotagmin-SNARE interactions and reveal unsuspected similarities between synaptotagmins and viral fusion proteins.

Myotonic dystrophy is caused by expanded CTG repeats, and the expression of these repeats as RNA leads to the sequestration of the splicing factor muscleblind-like (MBNL1) to the CUG RNA. Two mouse models for myotonic dystrophy—mice expressing expanded CUG repeats and mice lacking functional MBNL1—now reveal ∼100 new mis-splicing events and a new class of aberrantly regulated mRNAs.