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Protein Structure, Tertiary (4):
Recent article
Protein Structure, Tertiary
Abstract
We show that MyBP-C slow comprises a family of phosphoproteins. Ser-59 and Ser-62 are substrates for PKA, while Ser-83 and Thr-84 are substrates for PKC. Moreover, Ser-204 is substrate for both PKA and PKC. Importantly, the levels of phosphorylated skeletal MyBP-C proteins (i.e. slow and fast) are n...
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PMID: 21888435
PDF is available here.
PDF is available here.
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Abstract
We determined the high-resolution crystal structures of the EV71 3C(pro)/rupintrivir complex, showing that although rupintrivir interacts with EV71 3C(pro) similarly to HRV 3C(pro), the C terminus of the inhibitor cannot accommodate the leaving-group pockets of EV71 3C(pro). Our structures reveal th...
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PMID: 21813612
PDF is available here.
PDF is available here.
Abstract
We report here that a short N-terminal region of the medium subunit (PduD) is required for packaging the coenzyme B(12)-dependent diol dehydratase (PduCDE) into the lumen of the Pdu MCP. Analysis of soluble cell extracts and purified MCPs by Western blotting showed that the PduD subunit mediated pac...
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PMID: 21821773
PDF is available here.
PDF is available here.
Abstract
We show that homozygous disruption of PHD-1 (PHD-1(-/-)) could facilitate HIF-1α-mediated cardioprotection in ischemia/reperfused (I/R) myocardium. Wild-type (WT) and PHD-1(-/-) mice were randomized into WT time-matched control (TMC), PHD-1(-/-) TMC (PHD1TMC), WT I/R, and PHD-1(-/-) I/R (PHD1IR). I...
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PMID: 21083501
PDF is available here.
PDF is available here.
Abstract
We elaborate currently known information about Ad malfunction and deficiency pertaining to cardiovascular disease risk (including atherosclerosis, endothelial dysfunction, and cardiac injury), as well as review evidence supporting Ad resistance as a novel risk factor for cardiovascular injury, provi...
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PMID: 21091079
PDF is available here.
PDF is available here.
Abstract
We purified each individual NEAT domain of IsdX2 as a GST fusion and analyzed the specific function of each domain as it relates to heme acquisition and transport. NEAT domains 1, 3, 4, and 5 all bind heme, with domain 5 having the highest affinity. All NEATs associate with hemoglobin, but only NEAT...
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PMID: 21808055
PDF is available here.
PDF is available here.
Abstract
We have investigated which portion of Tg is engaged in this late stage of its maturation. First, we demonstrate that this event is linked to oxidation involving region I. Introduction of the Tg-C1245R mutation in the hinge (identical to that causing human goitrous hypothyroidism) inhibits this matur...
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PMID: 21816825
PDF is available here.
PDF is available here.
Abstract
We show that KLHL7 forms a dimer, assembles with Cul3 through its BTB and BACK domains, and exerts E3 activity. Lys-48-linked but not Lys-63-linked polyubiquitin chain co-localized with KLHL7, which increased upon proteasome inhibition suggesting that KLHL7 mediates protein degradation via UPS. An a...
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PMID: 21828050
PDF is available here.
PDF is available here.
Abstract
We identify a previously unknown target of POA as the ribosomal protein S1 (RpsA), a vital protein involved in protein translation and the ribosome-sparing process of trans-translation. Three PZA-resistant clinical isolates without pncA mutation harbored RpsA mutations. RpsA overexpression conferred...
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PMID: 21835980
PDF is available here.
PDF is available here.
Abstract
We now report the design and characterization of three single-site mutants of CD4D12 (G6A, L51I, and V86L) and one multisite mutant of CD4D1 (G6A/L51I/L5K/F98T). G6A, L51I, and V86L are cavity-filling mutations while L5K and F98T are surface mutations which were introduced to minimize the aggregatio...
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PMID: 21827143
PDF is available here.
PDF is available here.
Abstract
We review evidence that the lipid-exposed surfaces of membrane proteins have generally evolved to maintain correct structure and function in the face of major changes in lipid composition. Such tolerance has allowed evolution to extensively remodel membrane lipid compositions during the emergence of...
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PMID: 21848311
PDF is available here.
PDF is available here.
Abstract
We show that Rrn7, a subunit of the yeast Pol I core factor, and its human ortholog TAF1B are TFIIB-like factors. Although distantly related, Rrn7 shares many activities associated with TFIIB-like factors. Domain swaps between TFIIB-related factors show that Rrn7 is most closely related to the Pol I...
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PMID: 21921198
PDF is available here.
PDF is available here.
Abstract
We report that TAF1B, a subunit of human Pol I basal transcription factor SL1, is structurally related to TFIIB/TFIIB-like proteins, through predicted amino-terminal zinc ribbon and cyclin-like fold domains. SL1, essential for Pol I recruitment to the ribosomal RNA gene promoter, also has an essenti...
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PMID: 21921199
PDF is available here.
PDF is available here.
Abstract
We show that CUP employs multiple mechanisms to repress the expression of target mRNAs. In addition to inducing translational repression, CUP maintains mRNA targets in a repressed state by promoting their deadenylation and protects deadenylated mRNAs from further degradation. Translational repressio...
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PMID: 21937713
PDF is available here.
PDF is available here.
Abstract
We show that a LIM domain protein, Espinas (Esn), binds to an intracellular juxtamembrane domain of Flamingo (Fmi), and that this Fmi-Esn interplay elicits repulsion between dendritic branches of Drosophila sensory neurons. In wild-type larvae, branches of the same class IV dendritic arborization ne...
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PMID: 21937715
PDF is available here.
PDF is available here.
Abstract
We show that molecular interactions, e.g., protein-DNA interactions, can be analyzed in a directly analogous manner and with similarly remarkable results. Specifically, mesoscopic molecular interactions act as incoherent sensors that measure the energies of microscopic interactions between atoms. We...
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PMID: 21825146
PDF is available here.
PDF is available here.
Abstract
We obtained an all-atom model structure for the high-affinity form of MTBD bound to MT by an anisotropic network model, protein-protein docking, and molecular dynamics simulations. We observe that the magnitude of the coiled-coil helix sliding is dramatically reduced near the two prolines that form...
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PMID: 21809817
PDF is available here.
PDF is available here.
Abstract
Our structural data reveal that the FOG1-binding domain of GATA1, the N finger, can also directly contact LMO2 and show that, despite the small size ( 50 residues) of the GATA1 N finger, both FOG1 and LMO2 can simultaneously bind this domain. LMO2 in turn can simultaneously contact both GATA1 and t...
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PMID: 21844373
PDF is available here.
PDF is available here.
Abstract
We determined the structure of Phytophthora capsici AVR3a4, a close homolog of P. infestans AVR3a. Our structural and functional analyses reveal that the effector domain of AVR3a contains a conserved, positively charged patch and that this region, rather than the RXLR domain, is required for binding...
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PMID: 21821794
PDF is available here.
PDF is available here.
Abstract
We examine such coupling, and its unexpected complexity, using nearly full-length epidermal growth factor receptor (EGFR) and negative-stain EM. The liganded, dimeric EGFR ectodomain can couple both to putatively active, asymmetrically associated kinase dimers and to putatively inactive, symmetrical...
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PMID: 21822280
PDF is available here.
PDF is available here.
Abstract
We found that RNF4 bound ubiquitin-charged UbcH5a tightly but free UbcH5a weakly. To provide insight into the mechanism of RING-mediated ubiquitylation, we docked the UbcH5~ubiquitin thioester onto the RNF4 RING structure. This revealed that with E2 bound to one monomer of RNF4, the thioester-linked...
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PMID: 21857666
PDF is available here.
PDF is available here.
Abstract
We describe crystallographic and biochemical analyses of filament nucleation by VopL. The WH2 element of VopL does not nucleate on its own and requires the VCD for activity. The VCD forms a U-shaped dimer in the crystal, stabilized by a terminal coiled coil. Dimerization of the WH2 motifs contribute...
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PMID: 21873984
PDF is available here.
PDF is available here.
Abstract
The LINE-1 (L1) retrotransposon emerges as a major source of human interindividual genetic variation, with important implications for evolution and disease. L1 retrotransposition is poorly understood at the molecular level, and the mechanistic details and evolutionary origin of the L1-encoded L1ORF1...
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PMID: 21822284
PDF is available here.
PDF is available here.
Abstract
We have previously identified the ter operon (terXYW and terZABCDEF) of the uropathogenic strain Escherichia coli KL53. In this study, we use an innovative approach to identify putative protein-protein interaction partners for one of the essential tellurite resistance proteins - TerB. We observe tha...
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PMID: 21952438
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1814)9 2011
Abstract
We designed a novel VLR protein (called dVLR) containing six LRR repeats based on a sea lamprey receptor sequence. The designed protein was expressed in Escherichia coli in a soluble, native form and showed very favorable biophysical properties. Recombinant dVLR is monomeric in solution and preserve...
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PMID: 21621013
PDF is available here.
PDF is available here.
Circulation (124)8 2011
Abstract
We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dos...
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PMID: 21810665
PDF is available here.
PDF is available here.
Abstract
We recently introduced the enhanced aromatic sequon as a family of portable structural motifs that are stabilized upon glycosylation in specific reverse turn contexts: a five-residue type I β-turn harboring a G1 β-bulge (using a Phe-Yyy-Asn-Xxx-Thr sequon) and a type II β-turn within a six-residu...
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PMID: 21825145
PDF is available here.
PDF is available here.
Abstract
We have used single-molecule force spectroscopy in combination with molecular dynamics simulations to characterize the mechanics of the myomesin dimer comprising immunoglobulin domains My12-My13. We find that at forces of approximately 30 pN the α-helical linker reversibly elongates allowing the m...
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PMID: 21825161
PDF is available here.
PDF is available here.
Abstract
We show here that DNA binding to the DNA-gate of gyrase and wrapping of DNA around the C-terminal domains of GyrA induces a narrowing of the N-gate. This half-closed state prepares capture of a T-segment in the upper cavity of gyrase. Subsequent N-gate closure upon binding of ATP then poises the rea...
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PMID: 21817063
PDF is available here.
PDF is available here.
Abstract
We determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Å resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-l...
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PMID: 21822288
PDF is available here.
PDF is available here.
Abstract
We report the crystal structure of a motor domain dimer in complex with its tail domain at 2.2 angstroms and compare it with a structure of the motor domain alone at 2.7 angstroms. These structures indicate that neither an induced conformational change nor steric blocking is the cause of inhibition....
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PMID: 21836017
PDF is available here.
PDF is available here.
Abstract
We found that KIF1A, an axonal transporter of synaptic vesicles, interacts with the domain encoded by the HSN2 exon. In parallel to this screen, we performed genome-wide homozygosity mapping in a consanguineous Afghan family affected by HSANII and identified a unique region of homozygosity located o...
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PMID: 21820098
PDF is available here.
PDF is available here.
Abstract
We show that JH2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in JAK2: Ser523 and Tyr570. Inactivation of JH2 catalytic activity increased JAK2 basal activity and downstream signaling. Notably, different MPN mutations abrogated JH2 activity in cells, and in...
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PMID: 21841788
PDF is available here.
PDF is available here.
Developmental Cell (21)2 2011
Abstract
We show that the kinesin-like myosin passenger-protein Smy1 interacts with the FH2 domain of the formin Bnr1 to decrease rates of actin filament elongation, which is distinct from the formin displacement activity of Bud14. In vivo analysis of smy1Δ mutants demonstrates that this "damper" mechanism...
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PMID: 21839918
PDF is available here.
PDF is available here.
Developmental Cell (21)2 2011
Abstract
We show that selective autophagy downregulates Ty1 transposition by eliminating Ty1 VLPs from the cytoplasm under nutrient-limited conditions. Ty1 VLPs are targeted to autophagosomes by an interaction with Atg19. We propose that selective autophagy safeguards genome integrity against excessive inser...
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PMID: 21839922
PDF is available here.
PDF is available here.
Abstract
We report the design and synthesis of two compounds named pitstops that selectively block endocytic ligand association with the clathrin TD as confirmed by X-ray crystallography. Pitstop-induced inhibition of clathrin TD function acutely interferes with receptor-mediated endocytosis, entry of HIV, a...
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PMID: 21816279
PDF is available here.
PDF is available here.
Molecular Cell (43)3 2011
Abstract
We have biochemically reconstituted two distinct populations of nucleosomes containing Saccharomyces cerevisiae CenH3 (Cse4). Reconstitution of octameric nucleosomes containing histones Cse4/H4/H2A/H2B is robust on noncentromere DNA, but inefficient on AT-rich centromere DNA. However, nonhistone Scm...
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PMID: 21816344
PDF is available here.
PDF is available here.
Abstract
CCL5 (RANTES) is a proinflammatory chemokine known to activate leukocytes through its receptor, CCR5. Although the monomeric form of CCL5 is sufficient to cause cell migration in vitro, CCL5's propensity for aggregation is essential for migration in vivo, T cell activation and apo...
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PMID: 21827949
PDF is available here.
PDF is available here.
Abstract
We identified deleterious heterozygous mutations in ANKRD11 encoding ankyrin repeat domain 11, also known as ankyrin repeat-containing cofactor 1. A splice-site mutation, c.7570-1G>C (p.Glu2524_Lys2525del), cosegregated with the disease in a family with three affected members, whereas in a simplex c...
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PMID: 21782149
PDF is available here.
PDF is available here.
Crystal structure of reovirus attachment protein sigma1 in complex with sialylated oligosaccharides.
Abstract
We determined the crystal structures of reovirus attachment protein σ1 in complex with α-2,3-sialyllactose, α-2,6-sialyllactose, and α-2,8-di-siallylactose. All three oligosaccharides terminate in sialic acid, which serves as a receptor for the reovirus serotype studied here. The overall structu...
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PMID: 21829363
PDF is available here.
PDF is available here.
Abstract
We address this challenge, developing a new methodology for analysing and quantifying image data and its integration with biophysical models. Specifically we fit a binding kinetics model to 2 colour fluorescence data for cytoskeleton independent synapses (2 and 3D) and test whether the observed inve...
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PMID: 21829338
PDF is available here.
PDF is available here.
Abstract
We have shown that snakes co-opt a non-heat-sensitive channel, vertebrate TRPA1 (transient receptor potential cation channel A1), to produce an infrared detector. Here we show that vampire bats tune a channel that is already heat-sensitive, TRPV1, by lowering its thermal activation threshold to abou...
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PMID: 21814281
PDF is available here.
PDF is available here.
Abstract
We show that a previously uncharacterized member of the I-BAR subfamily, Pinkbar, is specifically expressed in intestinal epithelial cells, where it localizes to Rab13-positive vesicles and to the plasma membrane at intercellular junctions. Notably, the BAR domain of Pinkbar does not induce membrane...
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PMID: 21743456
PDF is available here.
PDF is available here.
Abstract
We have identified mutations in the gene MAN1B1, encoding a mannosyl oligosaccharide, alpha 1,2-mannosidase. In one Pakistani family, MR43, a homozygous nonsense mutation (RefSeq number NM_016219.3: c.1418G>A [p.Trp473(∗)]), segregated with intellectual disability and additional dysmorphic feature...
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PMID: 21763484
PDF is available here.
PDF is available here.
Abstract
We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. H...
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PMID: 21814488
PDF is available here.
PDF is available here.
Abstract
We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1...
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PMID: 21814493
PDF is available here.
PDF is available here.
Abstract
We show that AID inhibits the catalytic function by restraining the KD into an unproductive open conformation, thereby limiting local structural rearrangements, while mutations that disrupt the interactions between the KD and AID allow for both the local structural rearrangement and global interlobe...
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PMID: 21814500
PDF is available here.
PDF is available here.
Abstract
We perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function...
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PMID: 21814507
PDF is available here.
PDF is available here.
Abstract
We present the crystal structures of the SECRET domain of vTNFR CrmD encoded by ectromelia virus and its complex with chemokine CX3CL1. The SECRET domain adopts a β-sandwich fold and utilizes its β-sheet I surface to interact with CX3CL1, representing a new chemokine-binding manner of viral CKBPs....
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PMID: 21829356
PDF is available here.
PDF is available here.
Abstract
Abstract Expansions of sequence databases driven by new sequencing technology continue apace. These result in a continuous supply of protein sequences and domains that cannot be straightforwardly annotated by simple homology methods. For these, structure-based function prediction may...
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PMID: 21348639
PDF is available here.
PDF is available here.
Abstract
We determined the crystal structures of the P domain protein of the first Lewis-binding norovirus (VA207, GII.9) that has a distinct binding property from those of Norwalk virus and VA387. Co-crystallization of the VA207 P dimer with Le(y) or sialyl Le(x) tetrasaccharides showed that VA207 interacts...
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PMID: 21811409
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1814)7 2011
Abstract
We present the solution structure of GIP in membrane-mimicking environments by proton NMR spectroscopy and molecular modelling. GIP adopts an α-helical conformation between residues Phe(6)-Gly(31) and Ala(13)-Gln(29) for micellar and bicellar media, respectively. Previously we examined the effect o...
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PMID: 21539943
PDF is available here.
PDF is available here.
Abstract
Abstract
We report here that clusters of charged amino acids in the TR hormone-binding domain are required for this enhanced mode of coactivator recruitment and that mutations in these charge clusters, by disrupting TRβ2 coactivator binding, are a molecular basis for pituitary resistance to thyroid hormone,...
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PMID: 21622532
PDF is available here.
PDF is available here.
Biochimica et Biophysica Acta (1810)9 2011
Abstract
The mannose 6-phosphate receptor homology (MRH) domain-containing family of proteins, which include recycling receptors (mannose 6-phosphate receptors, MPRs), resident endoplasmic reticulum (ER) proteins (glucosidase II β-subunit, XTP3-B, OS-9), and a Golgi glycosyltransferase (GlcNAc-phosphotransfe...
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PMID: 21723917
PDF is available here.
PDF is available here.
Abstract
We have previously identified ADAMTSL2 mutations in a subset of GD patients. After exome sequencing in GD and AD cases, we selected fibrillin 1 (FBN1) as a candidate gene, even though mutations in this gene have been described in Marfan syndrome, which is characterized by tall stature and arachnodac...
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PMID: 21683322
PDF is available here.
PDF is available here.
Abstract
We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes a...
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PMID: 21664997
PDF is available here.
PDF is available here.
Abstract
We show that TRAMP inherently suppresses poly(A) addition after only 3-4 adenosines. This poly(A) tail length restriction is controlled by Mtr4p. The helicase detects the number of 3'-terminal adenosines and, over several adenylation steps, elicits precisely tuned adjustments of ATP affinities and r...
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PMID: 21663793
PDF is available here.
PDF is available here.
Abstract
We have studied the L24A mutant that has been shown previously to form non-native interactions in the folding transition state. A suite of Carr-Purcell-Meiboom-Gill relaxation dispersion NMR experiments have been used to measure backbone chemical shifts and amide bond vector orientations of the invi...
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PMID: 21639149
PDF is available here.
PDF is available here.
Abstract
We also predict that Glu15, Lys43, and Tyr46 may be important in the catalytic efficiency and thermostability of enzyme. The new structural and mechanistic insights obtained from computational study should be valuable for detailed structures and mechanisms of the member of the DJ-1 superfamily....
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PMID: 20711794
PDF is available here.
PDF is available here.