Volume 27 Issue 1, January 2020

A study reports the structures of membrane-bound flavin-containing monooxygenases (FMOs), solved using reconstructed ancestral mammalian FMOs. The models provide a structural basis for these enzymes’ mechanism of action and show how the proteins interact with membranes and how substrates access their active sites.

Microbially derived peptides that mimic immunogenic gliadin peptides in celiac disease have been identified using a structure- and sequence-guided search. T cell activation assays and crystal structures reveal that a protein from the commensal bacterium Pseudomonas fluorescens can be processed and presented by antigen-presenting cells to potently activate T cells from patients with celiac disease.

The cryo-EM structure of the PWWP reader domain of the transcriptional coactivator LEDGF in complex with an H3K36-methylated nucleosome reveals multivalent binding of the reader domain to the methylated histone tail and to both gyres of nucleosomal DNA.

Ancestral reconstruction leads to characterization and crystallization of three ancient mammalian flavin-containing monooxygenases, offering insights into their mechanisms of membrane binding, catalytic activity and substrate selection.

The crystal structure of a posttermination 70S ribosome complex with EF-G, RRF and two tRNAs bound reveals the active roles played by those factors in ribosome splitting and recycling.

Cryo-EM structures of human ATP-citrate lyase alone or bound to substrates or products and supportive biochemical and biophysical data reveal the catalytic mechanism of this enzyme, which is the major source of cytosolic acetyl-CoA.

Cryo-EM and functional analyses of human CTP synthase 2 reveal that this enzyme forms polymeric filaments that can switch between active and inactive forms, in response to substrate and product levels, resulting in highly cooperative regulation.

Structural, biochemical and cellular analyses show that bacterial antigens can mimic gliadin epitopes involved in celiac disease being presented by HLA-DQ2.5 and recognized by T cells derived from patients.

Cryo-EM structure of human transporter ABCB4 that extrudes phosphatidylcholine into the bile canaliculi suggests an ‘alternating access’ mechanism of lipid extrusion, distinct from the ‘credit card swipe’ model of other lipid transporters.

Cryo-EM structures of E. coli RecBCD complex with different DNA fork templates containing a Chi sequence reveal the conformational changes upon Chi recognition.

Cryo-EM structures of human SERINC5 and its fly orthologue, along with extensive functional analyses, reveal the protein architecture and identify regions important for HIV-1 restriction.

Receptors from the delta family of ionotropic glutamate receptors (iGluRs) differ from other iGluRs in that they are not gated by glutamate. Cryo-EM structures of the rat orphan GluD1 receptor also reveal a distinct, non-swapped architecture.

Deep mutational scanning data for multiple kinases reveal generalizable residues that mediate activity and drug resistance across the mammalian kinome.