Showing papers in "Structure in 2017"

TL;DR: The latest work on structural characterization of the checkpoint proteins, their interactions with cognate ligands and with therapeutic antibodies reveals that they all have a similar modular structure, composed of small domains similar in topology to the domains found in antibodies.

TL;DR: The Worldwide PDB recently launched a deposition, biocuration, and validation tool: OneDep, which provides useful metrics with which depositors can evaluate the quality of the experimental data, the structural model, and the fit between them.

TL;DR: The structure of a thermostabilized human A1 receptor at 3.3 Å resolution with PSB36, an A1-selective xanthine-based antagonist is reported, and the structural differences confirmed to lead to selectivity can be utilized in the design of new subtype- selective A1R or A2AR antagonists.

TL;DR: An atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database is presented, identifying 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories and providing a sequencing-to-molecular roadmap for examining microbiome- encoded enzymes essential to human health.

TL;DR: The crystallogenesis of a recombinantly produced membrane protein that never left a lipid bilayer environment is reported, as an alternative to approaches mediated by conventional detergents.

TL;DR: The design, functional operation, and supporting infrastructure of the OneDep system are described, and initial performance assessments are provided.

TL;DR: This structure provides the first atomic resolution snapshot of a human small HSP in functional state, explains how 14-3-3 proteins sequester their regulatory partners, and can inform the design of small-molecule interaction modifiers to be used as myorelaxants.

TL;DR: A spraying-plunging method for preparing cryoelectron microscopy grids with vitreous ice of controllable, highly consistent thickness using a microfluidic device is described and it is demonstrated that the structure can be solved to high resolution with this method of sample preparation.

TL;DR: This work comprehensively surveyed the specificity landscape of human SH3 domains in an unbiased manner using peptide-phage display and deep sequencing to reveal that roughly half of the Sh3 domains exhibit non-canonical specificities and collectively recognize a wide variety of peptide motifs, most of which were previously unknown.

TL;DR: The 2.6-Å resolution crystal structure of human APJR in complex with a designed 17-amino-acid apelin mimetic peptide agonist reveals that the peptides agonist adopts a lactam constrained curved two-site ligand binding mode.

TL;DR: Structural and biophysical insights are provided into the whole Cul2 complex that could aid future drug targeting and characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition.

TL;DR: The structural basis of AHR assembly and DNA interaction is established and provides a template for targeted drug design and mutational analyses prove the relevance of the observed interfaces for AHR-mediated gene activation.

TL;DR: Cryoelectron microscopy reconstructions of type IV pili from two important human pathogens, Pseudomonas aeruginosa and Neisseria gonorrhoeae, at ∼ 8 and 5 Å resolution are reported, which provide a framework for understanding T4P assembly, function, and biophysical properties.

TL;DR: A prototype system for depositing integrative/hybrid structural models, PDB-Development (PDB-Dev; https://pdb-dev.org) is public release.

TL;DR: A multi-technique study on constructs from the dimodular NRPS DhbF suggests that NRPSs lack a uniform, rigid supermodular architecture.

TL;DR: The structural dynamics information obtained in this study will guide future drug discovery against ZIKV and other flaviviruses.

TL;DR: It is revealed that the electrostatic interaction between the protein's charged residues and anionic lipids determines the K-Ras4A orientation, but that this is also influenced by the topology of the protein, reflecting the geometry of its surfaces.

TL;DR: The structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution is described and the molecular details of ligand-induced receptor dimerization, in particular of homotypic receptor interactions in immunoglobulin homology domains 4, 5, and 7 are revealed.

TL;DR: Cryoelectron tomography is used to visualize human mitoribosomes in isolated mitochondria and reveals a single major contact site with the inner membrane, mediated by the mitochondria-specific protein mL45.

TL;DR: These structures allow us to explore in detail the molecular recognition of ivermectin by GlyRs, GABAARs, and α7 nAChRs and hold promise in structure-based design of GlyR modulators for the treatment of neuropathic pain.

TL;DR: This work describes selective and potent inhibition of prolyl-tRNA synthetases (PRSs) from the above parasites using a series of quinazolinone-scaffold compounds and offers insights into the structure-guided optimization of quinazolinones for drug development against multiple human eukaryotic pathogens.

TL;DR: It is reported that members of the Src family of kinases (SFK) share well-conserved sequence features involving aromatic residues in their Unique domains, and it is argued that the Unique domain of each SFK is sensitive to specific input signals, but the entire family shares a common mechanism for connecting the disordered and structured domains.

TL;DR: These structures demonstrate an extensive structural heterogeneity of interface AFs that likely regulates subunit joining during 40S maturation and suggest that maturation of the 18S 3' end is regulated by dissociation of the AF Dim1 from the subunit interface, consistent with previous biochemical analyses.

TL;DR: The guanidine-I riboswitch is a conserved RNA element with approximately 2,000 known examples across four phyla of bacteria that exists upstream of nitrogen metabolism and multidrug resistance transporter genes and alters expression through the specific recognition of a free guanidinium cation.

TL;DR: This work reports, for the first time, the use of a supervised molecular dynamics approach to explore the possible protein-peptide binding pathways within a timescale reduced up to three orders of magnitude compared with classical molecular dynamics.

TL;DR: This study provides a dynamic structural insight into K2P channel mechanosensitivity and illustrates how the structure of a eukaryotic mechanosensitive ion channel responds to changes in forces within the bilayer.

TL;DR: A methodology that combines the high sensitivity afforded by nuclear magnetic resonance relaxation techniques and single-site multiple mutations to identify two allosterically coupled dynamic networks within the non-coherently dynamic enzyme cyclophilin A confirms a link between enzyme dynamics and the catalytic cycle of cyclophILin A and demonstrates how dynamic allostery may be engineered to tune enzyme function.

TL;DR: It is shown that ATP hydrolysis and assembly of the entire T1SS complex is necessary for protein secretion, and a 3.15-Å crystal structure of AaPrtD, the ABC transporter found in the Aquifex aeolicus T1 SS, supports a polypeptide transport mechanism distinct from alternating access.

TL;DR: Near-atomic resolution structures of the HPV16 capsid and HPV16 in complex with heparin are presented, both determined from cryoelectron micrographs collected with direct electron detection technology, clarifying details of capsid architecture for the first time.

TL;DR: Evidence is provided that ATP-dependent head-head engagement induces a lever movement of the SMC neck region, which might help to separate juxtaposed coiled-coil arms.