Volume 29 Issue 1, January 2022

Iboxamycin (IBX) is a new oxepanoprolinamide antibiotic based on clindamycin. Crystal structures of IBX in complex with bacterial ribosomes uncover the structural mechanism of its activity against multidrug-resistant pathogens and reveal key interactions with tRNAs and 23S rRNA, including resistance-conferring rRNA methylations.

An elegant cryo-EM and biophysical study unveils the conformational changes of the E. coli MutS mismatch repair factor. This provides a nice follow-up to the recent report from the same group characterizing how MutS scans DNA without initiating repair on correctly base-paired DNA and recruits MutL upon encountering a mismatch.

Retinal photoreceptor cyclic nucleotide-gated (CNG) ion channels convert light signals to electrical signals in the eye. Their structures have been solved at ~3 Å resolution by cryo-EM; the asymmetric subunit assembly of heteromeric CNG channels produces a unique ion-permeation pathway with an unusual gating apparatus that indicates distinct subunit contributions for ligand-dependent channel activation.

A cryo-EM structure of the Dbf4-dependent kinase (DDK) in the act of phosphorylating an Mcm2-7 helicase complex reveals how DDK selectively targets DNA-loaded MCM double hexamers to trigger replication origin activation. Checkpoint kinase Rad53 blocks origin firing by impairing double hexamer engagement by DDK.

New data reveal a sequential mode of alternative polyadenylation. Distal polyA sites are processed first and the resultant transcripts are retained in the nuclear-chromatin matrix for subsequent cleavage and polyadenylation at proximal polyA sites.

The cryo-EM structure of the bovine rod CNG channel, isolated from retina, sheds light onto the structural basis for the subunit stoichiometry and reveals an additional gate within the ion conduction pathway contributed by the CNGB1 subunit.

A cryo-EM structure of the human cone photoreceptor CNG channel reveals an odd subunit stoichiometry and unique structural features conferred by a distinct subunit, providing a framework to study cone CNG channel physiology and channelopathies.

A series of cryo-EM structures of human IMPDH1 variants reveal polymorphic filaments. Blindness-associated mutations in IMPDH1 are characterized and half disrupt feedback inhibition. Together, these findings are a foundation for understanding IMPDH1 in retinal function and disease.

Cryogenic electron microscopy structures of Escherichia coli MutS at sequential stages of the ATP hydrolysis cycle reveal how ATP binding and hydrolysis and its modulation by DNA enable MutS to adopt different conformations during mismatch repair.

The authors show that the Salmonella effector SopF is activated by ARF GTPases to ADP-ribosylate a glutamine in the V-ATPase subunit ATP6V0C, blocking xenophagy or other selective autophagy types independent of proton-pumping activity.