PMCID stringlengths 10 10 | Title stringlengths 46 162 | FullText stringlengths 17.4k 118k |
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PMC4802042 | A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation | Mitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs). MAPK signalling efficiency and specificity is modulated by protein–protein interactions between individual MAPKs and the docking motifs in... |
PMC4968113 | Structural diversity in a human antibody germline library | To support antibody therapeutic development, the crystal structures of a set of 16 germline variants composed of 4 different kappa light chains paired with 4 different heavy chains have been determined. All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) ... |
PMC4854314 | RNA protects a nucleoprotein complex against radiation damage | Systematic analysis of radiation damage within a protein–RNA complex over a large dose range (1.3–25 MGy) reveals significant differential susceptibility of RNA and protein. A new method of difference electron-density quantification is presented.With the wide use of high-flux third-generation synchrotron sources, radia... |
PMC4792962 | A unified mechanism for proteolysis and autocatalytic activation in the 20S proteasome | Biogenesis of the 20S proteasome is tightly regulated. The N-terminal propeptides protecting the active-site threonines are autocatalytically released only on completion of assembly. However, the trigger for the self-activation and the reason for the strict conservation of threonine as the active site nucleophile remai... |
PMC4937829 | Visualizing chaperone-assisted protein folding | Challenges in determining the structures of heterogeneous and dynamic protein complexes have greatly hampered past efforts to obtain a mechanistic understanding of many important biological processes. One such process is chaperone-assisted protein folding, where obtaining structural ensembles of chaperone:substrate com... |
PMC4848761 | Predictive features of ligand‐specific signaling through the estrogen receptor | Some estrogen receptor‐α (ERα)‐targeted breast cancer therapies such as tamoxifen have tissue‐selective or cell‐specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell‐specific signaling and breast cancer cell proliferation, we synthesized 241 ERα ... |
PMC4869123 | Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide | IL-17A is a pro-inflammatory cytokine that has been implicated in autoimmune and inflammatory diseases. Monoclonal antibodies inhibiting IL-17A signaling have demonstrated remarkable efficacy, but an oral therapy is still lacking. A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through pha... |
PMC4841544 | Molecular Basis of Ligand-Dependent Regulation of NadR, the Transcriptional Repressor of Meningococcal Virulence Factor NadA | Neisseria adhesin A (NadA) is present on the meningococcal surface and contributes to adhesion to and invasion of human cells. NadA is also one of three recombinant antigens in the recently-approved Bexsero vaccine, which protects against serogroup B meningococcus. The amount of NadA on the bacterial surface is of dire... |
PMC4822561 | Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex | Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. For K. pneumoniae, this is the first high-resolution clea... |
PMC4850273 | Molecular Dissection of Xyloglucan Recognition in a Prominent Human Gut Symbiont | Polysaccharide utilization loci (PUL) within the genomes of resident human gut Bacteroidetes are central to the metabolism of the otherwise indigestible complex carbohydrates known as “dietary fiber.” However, functional characterization of PUL lags significantly behind sequencing efforts, which limits physiological un... |
PMC4896748 | Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome | Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2•GTP bound with sordarin. The structures suggest a trajectory of IRES transloca... |
PMC4832331 | Structural insights into the Escherichia coli lysine decarboxylases and molecular determinants of interaction with the AAA+ ATPase RavA | The inducible lysine decarboxylase LdcI is an important enterobacterial acid stress response enzyme whereas LdcC is its close paralogue thought to play mainly a metabolic role. A unique macromolecular cage formed by two decamers of the Escherichia coli LdcI and five hexamers of the AAA+ ATPase RavA was shown to counter... |
PMC4872110 | Ribosome biogenesis factor Tsr3 is the aminocarboxypropyl transferase responsible for 18S rRNA hypermodification in yeast and humans | The chemically most complex modification in eukaryotic rRNA is the conserved hypermodified nucleotide N1-methyl-N3-aminocarboxypropyl-pseudouridine (macpΨ) located next to the P-site tRNA on the small subunit 18S rRNA. While S-adenosylmethionine was identified as the source of the aminocarboxypropyl (acp) group more th... |
PMC4784909 | The Structural Basis of Coenzyme A Recycling in a Bacterial Organelle | Bacterial Microcompartments (BMCs) are proteinaceous organelles that encapsulate critical segments of autotrophic and heterotrophic metabolic pathways; they are functionally diverse and are found across 23 different phyla. The majority of catabolic BMCs (metabolosomes) compartmentalize a common core of enzymes to metab... |
PMC4857006 | Reversal of DNA damage induced Topoisomerase 2 DNA–protein crosslinks by Tdp2 | Mammalian Tyrosyl-DNA phosphodiesterase 2 (Tdp2) reverses Topoisomerase 2 (Top2) DNA–protein crosslinks triggered by Top2 engagement of DNA damage or poisoning by anticancer drugs. Tdp2 deficiencies are linked to neurological disease and cellular sensitivity to Top2 poisons. Herein, we report X-ray crystal structures o... |
PMC4795551 | Biochemistry and Crystal Structure of Ectoine Synthase: A Metal-Containing Member of the Cupin Superfamily | Ectoine is a compatible solute and chemical chaperone widely used by members of the Bacteria and a few Archaea to fend-off the detrimental effects of high external osmolarity on cellular physiology and growth. Ectoine synthase (EctC) catalyzes the last step in ectoine production and mediates the ring closure of the sub... |
PMC4850288 | Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* | Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first... |
PMC4918759 | Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity | ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the l... |
PMC4820378 | Template-dependent nucleotide addition in the reverse (3′-5′) direction by Thg1-like protein | Structures of Thg1-like proteins provide insight into the template-dependent nucleotide addition in the reverse (3′-5′) direction.All polynucleotide chain elongation reactions, whether with DNA or RNA, proceed in the 5′-3′ direction. This reaction involves the nucleophilic attack of a 3′-OH of the terminal nucleotide i... |
PMC4887326 | Structural insights into the regulatory mechanism of the Pseudomonas aeruginosa YfiBNR system | YfiBNR is a recently identified bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can seques... |
PMC4746701 | Crystal structure of SEL1L: Insight into the roles of SLR motifs in ERAD pathway | Terminally misfolded proteins are selectively recognized and cleared by the endoplasmic reticulum-associated degradation (ERAD) pathway. SEL1L, a component of the ERAD machinery, plays an important role in selecting and transporting ERAD substrates for degradation. We have determined the crystal structure of the mouse ... |
PMC4918766 | Mechanism of extracellular ion exchange and binding-site occlusion in the sodium-calcium exchanger | Na/Ca exchangers utilize the Na electrochemical gradient across the plasma membrane to extrude intracellular Ca, and play a central role in Ca homeostasis. Here, we elucidate their mechanisms of extracellular ion recognition and exchange through a structural analysis of the exchanger from Methanococcus jannaschii (NCX_... |
PMC4822050 | Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition | UHRF1 is an important epigenetic regulator for maintenance DNA methylation. UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown. Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the t... |
PMC4772114 | Structural basis for the regulation of enzymatic activity of Regnase-1 by domain-domain interactions | Regnase-1 is an RNase that directly cleaves mRNAs of inflammatory genes such as IL-6 and IL-12p40, and negatively regulates cellular inflammatory responses. Here, we report the structures of four domains of Regnase-1 from Mus musculus—the N-terminal domain (NTD), PilT N-terminus like (PIN) domain, zinc finger (ZF) doma... |
PMC4831588 | X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin | High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are needed to understand the molecular basis of Alzheimer’s disease and develop therapies. This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Aβ. The development of a peptid... |
PMC4871749 | The Taf14 YEATS domain is a reader of histone crotonylation | The discovery of new histone modifications is unfolding at startling rates, however, the identification of effectors capable of interpreting these modifications has lagged behind. Here we report the YEATS domain as an effective reader of histone lysine crotonylation – an epigenetic signature associated with active tran... |
PMC4888278 | Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand | The nuclear hormone receptor RORγ regulates transcriptional genes involved in the production of the pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This transcriptional activity of RORγ is modulated through ... |
PMC4786784 | An extended U2AF–RNA-binding domain recognizes the 3′ splice site signal | How the essential pre-mRNA splicing factor U2AF recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 a... |
PMC4880283 | Crystal Structures of Putative Sugar Kinases from Synechococcus Elongatus PCC 7942 and Arabidopsis Thaliana | The genome of the Synechococcus elongatus strain PCC 7942 encodes a putative sugar kinase (SePSK), which shares 44.9% sequence identity with the xylulose kinase-1 (AtXK-1) from Arabidopsis thaliana. Sequence alignment suggests that both kinases belong to the ribulokinase-like carbohydrate kinases, a sub-family of FGGY ... |
PMC4887163 | Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity | The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear... |
PMC4774019 | The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion | The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis... |
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