Articles in 2019

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.

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.

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.

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.

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 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.

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.

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.

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.

Bacterial T-boxes are regulatory mRNA regions that control the transcription or translation of factors involved in amino acid supply. T-boxes act by directly binding to non-aminoacylated tRNA in response to amino acid starvation. Three studies now capture three-dimensional structures of tRNA–T-box complexes and reveal a set of RNA features that are required for the recognition of specific tRNAs and modulation of gene expression.

Stabilization of the 3D genome architecture surrounding DNA lesions is critical for the maintenance of genome integrity. A new report by Ochs et al. shows how 53BP1 and RIF1 assemble a higher-order structure in the vicinity of damaged chromatin to protect it from unscheduled DNA-end resection.

Cryo-EM resolution of HIV-1 Env trimer bound to CD4 and a tyrosine-sulfated, coreceptor-mimicking antibody reveals two configurations of gp120–gp41 protomers that create asymmetric Env trimer conformations on the path to membrane fusion.

Oligomers of human αA-crystallin are characterized structurally via a hybrid approach, combining cryo-EM, cross-linking/mass spectrometry, NMR and modeling, providing insight into their dynamic behavior and heterogeneity and revealing that oxidized oligomers can also act as chaperones.

The cocrystal structure of the Nocardia farcinica ileS T-box in complex with its cognate tRNA illustrates how mRNA junctions can create specific binding sites for interacting RNAs.

The structure of human SMG1–SMG8–SMG9, a PI(3)K-related protein kinase complex central to mRNA surveillance, uncovers an InsP₆-binding site in the SMG1 kinase that is conserved in mTOR and important for kinase activity.

Cryo-EM structure of the C-terminal domain of human APOBEC3F in complex with HIV-1 Vif and CFBβ, along with functional analyses, reveals how Vif targets a host restriction protein.

Cryo-EM structures of MERS-CoV S glycoprotein trimer in complex with different sialosides reveal how the virus engages with sialylated receptors, providing insight into receptor specificity and selectivity.

Biochemical and structural analysis demonstrate that simultaneous detection of poly-lysine in the exit tunnel and poly(A) in the decoding center allows ribosomes to detect aberrant mRNAs, stall elongation and trigger downstream quality control pathways.

Finally, the architecture of the translocase of the mitochondrial outer membrane (TOM complex) is revealed, after 20 years of anticipation. Two groups have now determined the near-atomic structures of the TOM complex. These findings improve understanding of the mechanisms by which TOM facilitates the passage of about 1,000 different proteins from the cytosol into the mitochondria.