Walensky and colleagues use hydrocarbon stapling to stabilize HIV-1 MPER peptides in a helical conformation that mimics the viral epitope and that is recognized by broadly neutralizing anti-HIV antibodies. Cover design by Erin Dewalt, based on photograph by © blickwinkel / Alamy. pp 1058–1067

An AAV–gene targeting genomic map in human cells described by Deyle and colleagues reveals that homologous recombination occurs preferentially at sites where transcription and replication machineries converge. Cover by Erin Dewalt from map image by Ryan McVay/Photodisc/Thinkstock. PP 969–975

A global survey of SUMOylation in human cells by Vertegaal and colleagues uncovers highly interconnected functional clusters of SUMOylated proteins and extensive crosstalk between SUMO and other post-translational modifications. Cover art by Ivo A. Hendriks. pp 927–936

High-resolution crystal structures of the Thermus thermophiles 70S ribosome reported by Polikanov, Steitz and Innis reveal a network of ordered water molecules that indicate a pathway for proton transfer during peptide-bond formation. Cover image from PhotoAlto sas/Alamy. pp 787–793

PUF proteins are single-stranded RNA-binding proteins that contain multiple repeat elements, each of which contains a tripartite amino acid motif that dictates the identity of the targeted RNA base. Wickens and colleagues analyze the specificities of two dozen PUF proteins to create a palette of RNA specificities that can be used to design new proteins tailored to RNA targets. Cover image from Kasia75/iStock/Thinkstock. pp 732–738, News and Views p 653

VDACs mediate the flow of metabolites across the outer mitochondrial membrane to the cytosol. A Markov state model of mouse VDAC1 permeation by Grabe, Abramson and colleagues reveals that ATP permeates the channel via multiple, discrete states that intertwine, similar to stepping stones crossing a creek. Cover image of Laurel Creek, West Virginia, courtesy of Paul Shaw. pp 626–632, News and Views p 575

During spliceosome assembly, Prp24 acts as a chaperone for proper annealing of the catalytic U6 snRNA with U4 snRNA. Brow and colleagues present the structure of yeast Prp24 bound to the U6 RNA core. The cover image shows an autoradiogram of the sequencing gel that first identified yeast U6 RNA. Image courtesy of David Brow. pp 544–551, News and Views p 503

CLC-type H+Cl– exchangers are regulated by voltage and H+ and Cl– concentrations, but their gating mechanism remains poorly understood. Accardi and colleagues now find that CLC transport is regulated by two gates that are functionally linked through structural rearrangements outside of the ion transport pathway. Cover design by Erin Dewalt. pp 456–463

In this issue, we feature a Focus on Ubiquitin, comprising specially commissioned Reviews and Commentaries that discuss the roles of ubiquitin and ubiquitin-like protein modifications in essential cell signaling pathways, as well as the mechanisms by which these modifications are applied and substrate specificity is achieved. Cover design by Erin Dewalt. pp 289–345

Double Holliday junctions (dHJ) produced by homologous recombination during double-strand break repair must be separated enzymatically. In this issue, Thomä et al. present the crystal structure of a human TopIIIα-Rmi1 subcomplex and detail how topoisomerase is stimulated to promote dHJ decatenation. Image from Kohl-Photo/Alamy. pp 261–268

A long intergenic non-coding RNA, Firre, is shown by Rinn and colleagues to localize to its own chromosomal locus and distinct interacting trans-chromosomal loci, and to interact with nuclear matrix factor hnRNPU. Firre is proposed to function as a nuclear organization factor, modulating the topological organization of multiple chromosomes. Illustration by Erin Dewalt from a design by Sigrid Knemeyer. pp 198–206

The type 3 secretion systems of infectious bacteria use the needle-like injectisome to secrete virulence factors from the bacterial cytoplasm into host cells. Marlovits and colleagues use cryo-electron tomography and singleparticle cryo-electron microscopy to reveal the path of unfolded protein substrates through the injectisome. Illustration by Erin Dewalt from a cryo-EM image provided by Thomas Marlovits. pp 82–87