Search

Rossi and colleagues assemble an in vitro enzymatic pipeline using enzymes from distinct domains of life to recapitulate eukaryotic N-glycosylation. This work advances the synthesis of bespoke glycopeptides with biomedical and biotechnological applications.

Human MATE1 is a key transporter in kidney and liver drug clearance. Here, authors present cryo-EM structures of MATE1 in complex with substrates and an inhibitor, revealing the structural basis of drug recognition.

The structure of a putative molybdate transporter (ModB₂C₂) is presented in complex with its cognate binding protein ModA. These results help provide the structural basis for the ATP-driven transport mechanism of both clinically relevant multi-drug ABC exporters and of ABC importers facilitating bacterial nutrient uptake.

ABC transporters use ATP hydrolysis to translocate substrates across cell membranes. Kaspar Locher reviews the mechanistic diversity of ABC transporters, as has emerged from recent structural studies, and discusses future directions for investigation of ABC-transporter-catalyzed reactions.

Hepatitis B and D viruses require docking to the NTCP receptor protein for cell entry, an interaction that can be blocked by the drug bulevirtide. Here the authors use cryo-EM to reveal the structural basis of bulevirtide activity.

BSEP (ABCB11) is expressed in hepatocytes and extrudes bile salts into the canaliculi of the liver. Here, authors report cryo-EM structures of BSEP providing structural and functional insight into the mechanism of bile salt extrusion and small-molecule inhibition.

Oligosaccharyltransferase (OST), the central enzyme in N-glycosylation, modifies acceptor proteins by attaching a complex glycan. Cryo-EM structures of OST in distinct states, reveal the molecular basis of substrate recognition and catalysis.

Gram-negative bacteria use heme import systems to sequester heme from their environment. The structure of the ABC transporter HmuUV, the heme importer from Yersinia pestis, in the nucleotide-free, apo state was determined, revealing an outward-facing conformation for the transporter.

Analyses reveal a previously undescribed transmembrane protein fold in the endoplasmic reticulum-based glucosyltransferase ALG6 and provide a structural basis for understanding the glucose transfer mechanism.

A key step of drug metabolism in the human body is the uptake into liver cells, which is mediated by transport proteins of the OATP family. Here, authors report cryo-EM structures of two human OATP proteins, providing insight into their function.

Tryptophan C-mannosyltransferase (CMT) enzymes append a mannose to the first tryptophan of select sequences, which is important for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. A study reveals the structure, mode of peptide recognition and catalytic mechanism for the eukaryotic C-mannosyltransferase DPY19.

The X-ray crystal structure of the ABC transporter PglK, which facilitates the flipping of lipid-linked oligosaccharides (LLOs) in C. jejuni, in inward- and outward-facing states is solved; the structures and follow-up biochemical experiments support an unprecedented mechanism in which the polyprenyl tail of LLO remains partially embedded in the lipid bilayer, and the pyrophosphate-oligosaccharide head group is flipped into the outward-facing cavity after ATP is hydrolysed.

Oligosaccharyltransferases catalyse the transfer of lipid-anchored glycans onto acceptor asparagine residues in substrate proteins. By assaying chemically modified peptide substrate analogues, Lizak et al. rule out all but one of the currently postulated catalytic mechanisms for this enzyme.

Cellular uptake of vitamin B12 (cobalamin) requires the binding of holo-transcobalamin (TC) from plasma by CD320. Here, the authors report the structure of a complex between CD320 and TC loaded with cyanocobalamin, alongside additional functional analysis.

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.

A new crystal structure of BtuCD, a bacterial ABC transporter that uses ATP hydrolysis to drive vitamin B12 uptake, bound to an AMP-PNP nucleotide, completes the structural elucidation of intermediates in the transport cycle and reveals how ATP accelerates transport.

The X-ray crystal structure of the transporter-binding protein complex BtuCD–F, involved in the uptake of vitamin B₁₂ across the inner membrane of Escherichia coli, is determined in an ATP analogue-bound state; the membrane-spanning BtuC subunits adopt a previously unseen conformation in which the central translocation pathway is sealed by an additional gate, and membrane transport is seen to occur through an unexpected peristaltic transport mechanism, distinct from what has been observed for other ABC transporters.

ABCG2 is a transporter contributing to multidrug resistance of cancer cells. Here, structures of human ABCG2 under turnover conditions reveal distinct conformational states, provide insight into the transport cycle and suggest a mechanism of discrimination between substrates and inhibitors.

The structure of human ABCG2 bound to an inhibitory antibody using cryo-electron microscopy, representing the first high-resolution structural data of a human multidrug transporter.

The crystal structure of the single-subunit oligosaccharyltransferase PglB in complex with acceptor peptide and a synthetic lipid-linked oligosaccharide analog reveals a key intermediate in the reaction mechanism.

The glycosyltransferase PglH transfers three terminal N-acetylgalactosamine (GalNAc) residues to a carrier, which is a prerequisite for bacterial protein N-glycosylation. Here authors present the crystal structures of PglH in three distinct states and show that a ‘ruler helix’ facilitates membrane attachment and glycan counting.

Cryo-EM structures of human ABCG2 bound to synthetic derivatives of inhibitor Ko143 or the multidrug resistance modulator tariquidar together with insight into the structure–activity relationship of the Ko143 scaffold provide a basis for the design of novel ABCG2 inhibitors.

ABC transporters move substrates across the membrane. The substrate is often delivered by a binding protein. Functional analysis of the bacterial BtuCD-F system now reveals a distinct mechanism for substrate delivery different from other ABC transporters, whereby the binding protein associates with the transporter in the absence of substrate, and substrate or ATP binding destabilize the complex.

Cryo-electron microscopy structures of the ABCG2 protein in ATP- and substrate-bound states reveal the location of substrate binding, conformational changes required for substrate translocation and how inhibitors might be distinguished from substrates.