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- Author:
- Chu, Feixia; Hogan, Donna; Gupta, Richa; Gao, Xiong-Zhuo; Nguyen, Hieu T.; Cote, Rick H.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3677-3689
- ISSN:
- 0022-2836
- Subject:
- active sites; catalytic activity; cones (retina); crosslinking; cyclic GMP; enzymes; hydrolysis; ligands; mass spectrometry; mutation; protein subunits; retinal diseases
- Abstract:
- ... Photoreceptor phosphodiesterase (PDE6) is the central effector enzyme in the visual excitation pathway in rod and cone photoreceptors. Its tight regulation is essential for the speed, sensitivity, recovery, and adaptation of visual signaling. The rod PDE6 holoenzyme (Pαβγ₂) is composed of a catalytic heterodimer (Pαβ) that binds two inhibitory γ subunits. Each of the two catalytic subunits (Pα and ...
- DOI:
- 10.1016/j.jmb.2019.07.035
- PubMed:
- 31394113
- PubMed Central:
- PMC6733632
-
https://dx.doi.org/10.1016/j.jmb.2019.07.035
- Author:
- Koganitsky, Anna; Tworowski, Dmitry; Dadosh, Tali; Cecchini, Gary; Eisenbach, Michael
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3662-3676
- ISSN:
- 0022-2836
- Subject:
- Escherichia coli; anaerobiosis; bacteria; bacterial motility; electrostatic interactions; flavoproteins; fumarates; microscopy; succinate dehydrogenase (quinone)
- Abstract:
- ... Fumarate, an electron acceptor in anaerobic respiration of Escherichia coli, has an additional function of assisting the flagellar motor to shift from counterclockwise to clockwise rotation, with a consequent modulation of the bacterial swimming behavior. Fumarate transmits its effect to the motor via the fumarate reductase complex (FrdABCD), shown to bind to FliG—one of the motor’s switch protein ...
- DOI:
- 10.1016/j.jmb.2019.08.001
- PubMed:
- 31412261
- PubMed Central:
- PMC6733631
-
https://dx.doi.org/10.1016/j.jmb.2019.08.001
- Author:
- Das, Subhadeep; Biswas, Subir; Chaudhuri, Shouvik; Bhattacharyya, Arindam; Das, Biswadip
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3626-3646
- ISSN:
- 0022-2836
- Subject:
- Saccharomyces cerevisiae; exosomes; gene expression; messenger RNA; open reading frames; physiological transport
- Abstract:
- ... In Saccharomyces cerevisiae, a special class of mRNAs representing a subset of otherwise normal transcripts displays very slow export and an unusually long intra-nuclear dwell time. This prolonged nuclear retention leads to their rapid degradation in the nucleus by the nuclear exosome and DRN (Decay of RNA in the Nucleus) apparatus. We previously attributed their slow export to one or more hypothe ...
- DOI:
- 10.1016/j.jmb.2019.07.005
-
https://dx.doi.org/10.1016/j.jmb.2019.07.005
- Author:
- Federman, Ross S.; Boguraev, Anna-Sophia; Heim, Erin N.; DiMaio, Daniel
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3753-3770
- ISSN:
- 0022-2836
- Subject:
- amino acid sequences; amino acid substitution; erythropoietin; evolution; hydrophobicity; leucine; mice; oligomerization; platelet-derived growth factor; platelet-derived growth factor receptor beta; transmembrane proteins
- Abstract:
- ... Specific interactions between the helical membrane-spanning domains of transmembrane proteins play central roles in the proper folding and oligomerization of these proteins. However, the relationship between the hydrophobic amino acid sequences of transmembrane domains and their functional interactions is in most cases unknown. Here, we use ultra-simple artificial proteins to systematically study ...
- DOI:
- 10.1016/j.jmb.2019.07.009
- PubMed:
- 31301406
- PubMed Central:
- PMC6733641
-
https://dx.doi.org/10.1016/j.jmb.2019.07.009
- Author:
- Papadaki, Georgia F.; Lambrinidis, George; Zamanos, Andreas; Mikros, Emmanuel; Diallinas, George
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3827-3844
- ISSN:
- 0022-2836
- Subject:
- Aspergillus nidulans; allantoin; endocytosis; evolution; genetic analysis; lipids; molecular dynamics; pH; substrate specificity; transporters; uracil; uric acid
- Abstract:
- ... FurE, a member of the NCS1 family, is an Aspergillus nidulans transporter specific for uracil, allantoin and uric acid. Recently, we showed that C- or N-terminally truncated FurE versions are blocked for endocytosis and surprisingly show modified substrate specificities. Bifluorescence complementation assays and genetic analyses supported the idea that C- and N-termini interact dynamically and thr ...
- DOI:
- 10.1016/j.jmb.2019.07.013
-
https://dx.doi.org/10.1016/j.jmb.2019.07.013
- Author:
- Schmidhauser, Meret; Renz, Peter F.; Tsikrika, Panagiota; Freimann, Remo; Wutz, Anton; Wrana, Jeffrey L.; Beyer, Tobias A.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3920-3932
- ISSN:
- 0022-2836
- Subject:
- CRISPR-Cas systems; antibody specificity; chemical inhibitors; cyclin-dependent kinase; embryonic stem cells; gene editing; genes; phosphorylation; post-translational modification; serine; transcription factors
- Abstract:
- ... Modifications by kinases are a fast and reversible mechanism to diversify the function of the targeted proteins. The OCT4 transcription factor is essential for preimplantation development and pluripotency of embryonic stem cells (ESC), and its activity is tightly regulated by post-transcriptional modifications. Several phosphorylation sites have been identified by systemic approaches and their fun ...
- DOI:
- 10.1016/j.jmb.2019.07.015
-
https://dx.doi.org/10.1016/j.jmb.2019.07.015
- Author:
- Battistini, Federica; Hospital, Adam; Buitrago, Diana; Gallego, Diego; Dans, Pablo D.; Gelpí, Josep Lluis; Orozco, Modesto
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3845-3859
- ISSN:
- 0022-2836
- Subject:
- B-DNA; deformation; models
- Abstract:
- ... The rules governing sequence-specific DNA–protein recognition are under a long-standing debate regarding the prevalence of base versus shape readout mechanisms to explain sequence specificity and of the conformational selection versus induced fit binding paradigms to explain binding-related conformational changes in DNA. Using a combination of atomistic simulations on a subset of representative se ...
- DOI:
- 10.1016/j.jmb.2019.07.021
-
https://dx.doi.org/10.1016/j.jmb.2019.07.021
- Author:
- Javitt, Gabriel; Calvo, María Luisa Gómez; Albert, Lis; Reznik, Nava; Ilani, Tal; Diskin, Ron; Fass, Deborah
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3740-3752
- ISSN:
- 0022-2836
- Subject:
- amino acids; blood coagulation factors; crystal structure; dimerization; disulfide bonds; hemostasis; hydrogels; intestinal microorganisms; intestinal mucosa; models; mucins; polymerization; polymers; respiratory system
- Abstract:
- ... The mucin 2 glycoprotein assembles into a complex hydrogel that protects intestinal epithelia and houses the gut microbiome. A major step in mucin 2 assembly is further multimerization of preformed mucin dimers, thought to produce a honeycomb-like arrangement upon hydrogel expansion. Important open questions are how multiple mucin 2 dimers become covalently linked to one another and how mucin 2 mu ...
- DOI:
- 10.1016/j.jmb.2019.07.018
- PubMed:
- 31310764
- PubMed Central:
- PMC6739602
-
https://dx.doi.org/10.1016/j.jmb.2019.07.018
- Author:
- Abrusán, György; Marsh, Joseph A.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3871-3888
- ISSN:
- 0022-2836
- Subject:
- binding proteins; binding sites; chaperonins; computational methodology; evolution; ligands; stochastic processes
- Abstract:
- ... Ligand binding site structure has profound consequences for the evolution of function of protein complexes, particularly in homomers—complexes comprising multiple copies of the same protein. Previously, we have shown that homomers with multichain binding sites (MBSs) are characterized by more conserved binding sites and quaternary structure, and qualitatively different allosteric pathways than hom ...
- DOI:
- 10.1016/j.jmb.2019.07.014
- PubMed:
- 31306664
- PubMed Central:
- PMC6739599
-
https://dx.doi.org/10.1016/j.jmb.2019.07.014
- Author:
- Bernal, Ivonne; Börnicke, Jonathan; Heidemann, Johannes; Svergun, Dmitri; Horstmann, Julia A.; Erhardt, Marc; Tuukkanen, Anne; Uetrecht, Charlotte; Kolbe, Michael
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3787-3803
- ISSN:
- 0022-2836
- Subject:
- Gram-negative bacteria; Salmonella Typhimurium; adenosinetriphosphatase; mass spectrometry; pods; secretion; small-angle X-ray scattering; solubility; stoichiometry; tomography; type III secretion system
- Abstract:
- ... Many medically relevant Gram‐negative bacteria use the type III secretion system (T3SS) to translocate effector proteins into the host for their invasion and intracellular survival. A multi-protein complex located at the cytosolic interface of the T3SS is proposed to act as a sorting platform by selecting and targeting substrates for secretion through the system. However, the precise stoichiometry ...
- DOI:
- 10.1016/j.jmb.2019.07.004
-
https://dx.doi.org/10.1016/j.jmb.2019.07.004
- Author:
- Gordon, Jacob; Pillon, Monica C.; Stanley, Robin E.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3771-3786
- ISSN:
- 0022-2836
- Subject:
- catalytic activity; enzymes; humans; image analysis; internal transcribed spacers; motor neurons; phosphorylation; proteome; ribosomal RNA; ribosomes; translation (genetics)
- Abstract:
- ... The ribosome plays a universal role in translating the cellular proteome. Defects in the ribosome assembly factor Las1L are associated with congenital lethal motor neuron disease and X-linked intellectual disability disorders, yet its role in processing precursor ribosomal RNA (pre-rRNA) is largely unclear. The Las1L endoribonuclease associates with the Nol9 polynucleotide kinase to form the inter ...
- DOI:
- 10.1016/j.jmb.2019.07.007
- PubMed:
- 31288032
- PubMed Central:
- PMC6733650
-
https://dx.doi.org/10.1016/j.jmb.2019.07.007
- Author:
- Sharir-Ivry, Avital; Xia, Yu
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3860-3870
- ISSN:
- 0022-2836
- Subject:
- active sites; binding sites; catalytic activity; enzymes; ligands; protein-protein interactions; proteins; solvents
- Abstract:
- ... Enzymes exhibit a strong long-range evolutionary constraint that extends from their catalytic site and affects even distant sites, where site-specific evolutionary rate increases monotonically with distance. While protein–protein sites in enzymes were previously shown to induce only a weak conservation gradient, a comprehensive relationship between different types of functional sites in proteins a ...
- DOI:
- 10.1016/j.jmb.2019.07.019
-
https://dx.doi.org/10.1016/j.jmb.2019.07.019
- Author:
- Bhatia, Sandhya; Krishnamoorthy, G.; Dhar, Deepak; Udgaonkar, Jayant B.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3814-3826
- ISSN:
- 0022-2836
- Subject:
- Gibbs free energy; activation energy; amino acid sequences; energy transfer; evolution; fluorescence; light intensity; models; polymers; polypeptides; protein folding
- Abstract:
- ... To obtain proper insight into how structure develops during a protein folding reaction, it is necessary to understand the nature and mechanism of the polypeptide chain collapse reaction, which marks the initiation of folding. Here, the time-resolved fluorescence resonance energy transfer technique, in which the decay of the fluorescence light intensity with time is used to determine the time evolu ...
- DOI:
- 10.1016/j.jmb.2019.07.024
-
https://dx.doi.org/10.1016/j.jmb.2019.07.024
- Author:
- Tee, Wei-Ven; Guarnera, Enrico; Berezovsky, Igor N.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3933-3942
- ISSN:
- 0022-2836
- Subject:
- NADP-glucose-6-phosphate dehydrogenase; amino acid sequences; case studies; humans; mechanical models; phenotype; proteins; single nucleotide polymorphism; transferases
- Abstract:
- ... The molecular mechanisms of pathological non-synonymous single-nucleotide polymorphisms are still the object of intensive research. To this end, we explore here whether non-synonymous single-nucleotide polymorphisms can work via allosteric mechanisms. Using structure-based statistical mechanical model of allostery and analyzing energetics of the effects of mutations in a set of 27 proteins with at ...
- DOI:
- 10.1016/j.jmb.2019.07.012
-
https://dx.doi.org/10.1016/j.jmb.2019.07.012
- Author:
- Barklis, Eric; Stephen, Andrew G.; Staubus, August O.; Barklis, Robin Lid; Alfadhli, Ayna
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3706-3717
- ISSN:
- 0022-2836
- Subject:
- catalytic activity; cell membranes; humans; lipids; mutation; nanoparticles; neoplasms; post-translational modification; proteins
- Abstract:
- ... Mutations of the Ras proteins HRAS, KRAS4A, KRAS4B, and NRAS are associated with a high percentage of all human cancers. The proteins are composed of highly homologous N-terminal catalytic or globular domains, plus C-terminal hypervariable regions (HVRs). Post-translational modifications of all RAS HVRs helps target RAS proteins to cellular membrane locations where they perform their signaling fun ...
- DOI:
- 10.1016/j.jmb.2019.07.025
- PubMed:
- 31330153
- PubMed Central:
- PMC6733658
-
https://dx.doi.org/10.1016/j.jmb.2019.07.025
- Author:
- Führer, Sebastian; Tollinger, Martin; Dunzendorfer-Matt, Theresia
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3889-3899
- ISSN:
- 0022-2836
- Subject:
- GTPase-activating proteins; arginine; binding sites; central nervous system; cytosol; genes; genetic disorders; missense mutation; mutants; neoplasms; nuclear magnetic resonance spectroscopy; patients; risk; threonine
- Abstract:
- ... Neurofibromatosis type I (NF1) and Legius syndrome are rare inherited disorders that share diagnostic symptoms including dermal abnormalities like axillary and inguinal freckling and café au lait spots. In addition, patients suffering from NF1 have a demanding risk for the development of severe tumors of the peripheral and central nervous system among other NF1-specific symptoms. NF1 and Legius sy ...
- DOI:
- 10.1016/j.jmb.2019.07.038
-
https://dx.doi.org/10.1016/j.jmb.2019.07.038
- Author:
- Das, Tanuza; Kim, Eunice EunKyeong; Song, Eun Joo
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3900-3912
- ISSN:
- 0022-2836
- Subject:
- cyclin-dependent kinase; enzyme activity; enzyme inhibitors; fractionation; humans; mass spectrometry; phosphorylation; post-translational modification; sequence homology; spliceosomes; ubiquitinyl hydrolase 1
- Abstract:
- ... Deubiquitinating enzymes have key roles in diverse cellular processes whose enzymatic activities are regulated by different mechanisms including post-translational modification. Here, we show that USP15 is phosphorylated, and its localization and activity are dependent on the phosphorylation status. Nuclear-cytoplasmic fractionation and mass spectrometric analysis revealed that Thr149 and Thr219 o ...
- DOI:
- 10.1016/j.jmb.2019.07.023
-
https://dx.doi.org/10.1016/j.jmb.2019.07.023
- Author:
- Zhong, Wenhe; Guo, Jingjing; Cui, Liang; Chionh, Yok Hian; Li, Kuohan; El Sahili, Abbas; Cai, Qixu; Yuan, Meng; Michels, Paul A.M.; Fothergill-Gilmore, Linda A.; Walkinshaw, Malcolm D.; Mu, Yuguang; Lescar, Julien; Dedon, Peter C.
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3690-3705
- ISSN:
- 0022-2836
- Subject:
- Mycobacterium tuberculosis; binding sites; carbon; crystal structure; enzyme activity; glucose 6-phosphate; glycolysis; hypoxia; metabolome; pentose phosphate cycle; pentoses; pyruvate kinase; ribose
- Abstract:
- ... In response to the stress of infection, Mycobacterium tuberculosis (Mtb) reprograms its metabolism to accommodate nutrient and energetic demands in a changing environment. Pyruvate kinase (PYK) is an essential glycolytic enzyme in the phosphoenolpyruvate–pyruvate–oxaloacetate node that is a central switch point for carbon flux distribution. Here we show that the competitive binding of pentose mono ...
- DOI:
- 10.1016/j.jmb.2019.07.033
-
https://dx.doi.org/10.1016/j.jmb.2019.07.033
- Author:
- Karl, Martin; Sommer, Christian; Gabriel, Christian H.; Hecklau, Katharina; Venzke, Melanie; Hennig, Anna Floriane; Radbruch, Andreas; Selbach, Matthias; Baumgrass, Ria
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3606-3625
- ISSN:
- 0022-2836
- Subject:
- DNA; T-lymphocytes; epigenetics; gene editing; genes; histones; mass spectrometry; methyltransferases; transcription factors
- Abstract:
- ... Differentiation toward CD4⁺ regulatory T (Treg) cells is essentially dependent on an epigenetic program at Treg signature genes, which involves remodeling of the Treg-specific demethylated regions (TSDRs). In particular, the epigenetic status of the conserved non-coding sequence 2 of Foxp3 (Foxp3 TSDR) determines expression stability of the master transcription factor and thus Treg lineage identit ...
- DOI:
- 10.1016/j.jmb.2019.07.031
-
https://dx.doi.org/10.1016/j.jmb.2019.07.031
- Author:
- Kim, Jun Hoe; Kim, Bong Heon; Brooks, Shelby; Kang, Seung Yeon; Summers, Ryan M.; Song, Hyun Kyu
- Source:
- Journal of molecular biology 2019 v.431 no.19 pp. 3647-3661
- ISSN:
- 0022-2836
- Subject:
- Pseudomonas putida; biodegradation; caffeine; catalytic activity; demethylation; electron transfer; enzymatic reactions; fluorescent labeling; industrial applications; methylxanthines; oxygenases; small-angle X-ray scattering; soil bacteria; stoichiometry
- Abstract:
- ... Caffeine, found in many foods, beverages, and pharmaceuticals, is the most used chemical compound for mental alertness. It is originally a natural product of plants and exists widely in environmental soil. Some bacteria, such as Pseudomonas putida CBB5, utilize caffeine as a sole carbon and nitrogen source by degrading it through sequential N-demethylation catalyzed by five enzymes (NdmA, NdmB, Nd ...
- DOI:
- 10.1016/j.jmb.2019.08.004
-
https://dx.doi.org/10.1016/j.jmb.2019.08.004