Genomes and Genes
Summary: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
- Brogie J, Price D. Reconstitution of a functional 7SK snRNP. Nucleic Acids Res. 2017;45:6864-6880 pubmed publisher..Inhibition of MEPCE is dependent on the structure of the 3? stem loop and the closed form of 7SK RNA. This study provides important insights into intramolecular interactions within the 7SK snRNP...
- Tubiana T, Boulard Y, Bressanelli S. Dynamics and asymmetry in the dimer of the norovirus major capsid protein. PLoS ONE. 2017;12:e0182056 pubmed publisher..Our work brings new lights on the surprising conformational range encoded in the norovirus major capsid protein. ..
- Chereji R, Bharatula V, Elfving N, Blomberg J, Larsson M, Morozov A, et al. Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly. Nucleic Acids Res. 2017;45:8806-8821 pubmed publisher..This suggests that Mediator plays a significant role in higher-order genome organization. ..
- Knappenberger A, Grandhi S, Sheth R, Ahmad M, Viswanathan R, Harris M. Phylogenetic sequence analysis and functional studies reveal compensatory amino acid substitutions in loop 2 of human ribonucleotide reductase. J Biol Chem. 2017;292:16463-16476 pubmed publisher..These findings yield insight into loop 2's roles in regulating RR specificity, allostery, and oligomerization. ..
- Janda C, Dang L, You C, Chang J, de Lau W, Zhong Z, et al. Surrogate Wnt agonists that phenocopy canonical Wnt and ?-catenin signalling. Nature. 2017;545:234-237 pubmed publisher..Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine. ..
- Nevin P, Gabbai C, Marians K. Replisome-mediated translesion synthesis by a cellular replicase. J Biol Chem. 2017;292:13833-13842 pubmed publisher..These findings suggest that DNA damage at the replication fork can be replicated directly by the replisome without the need to activate error-prone pathways. ..
- Serrano S, Huarte N, Rujas E, Andreu D, Nieva J, Jimenez M. Structure-Related Roles for the Conservation of the HIV-1 Fusion Peptide Sequence Revealed by Nuclear Magnetic Resonance. Biochemistry. 2017;56:5503-5511 pubmed publisher..We conclude that, beyond hydrophobicity, preserving sequence order is an important feature for defining the secondary structures and oligomeric states adopted by the HIV FP in membranes. ..
- Wang J, Nikhil K, Viccaro K, Chang L, Jacobsen M, Sandusky G, et al. The Aurora-A-Twist1 axis promotes highly aggressive phenotypes in pancreatic carcinoma. J Cell Sci. 2017;130:1078-1093 pubmed publisher..This is the first study that links Twist1 in a feedback loop with its activating kinase, which indicates that concurrent inhibition of AURKA and Twist1 will be synergistic in inhibiting pancreatic tumorigenesis and metastasis. ..
- Diebold Durand M, Lee H, Ruiz Avila L, Noh H, Shin H, Im H, et al. Structure of Full-Length SMC and Rearrangements Required for Chromosome Organization. Mol Cell. 2017;67:334-347.e5 pubmed publisher..We show that this mechanochemical gating reaction regulates chromosome targeting and propose a mechanism for DNA translocation based on the merging of DNA loops upon closure of Smc arms. ..
- Pini L, Tiberio L, Venkatesan N, Bezzi M, Corda L, Luisetti M, et al. The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha-1 antitrypsin deficiency. Respir Res. 2014;15:112 pubmed publisher..01). Polymers of Z-alpha-1 antitrypsin form in bronchial epithelial cells, suggesting that these cells may be involved in the pathogenesis of lung emphysema and in bronchial epithelial cell dysfunction. ..
- Kubota H, Miyazaki M, Ogawa T, Shimozawa T, Kinosita K, Ishiwata S. Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization. Biophys J. 2017;113:461-471 pubmed publisher..Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization. ..
- Dias A, Rodrigues T, Pedrosa A, Barros Barbosa A, Francisco T, Azevedo J. The peroxisomal matrix protein translocon is a large cavity-forming protein assembly into which PEX5 protein enters to release its cargo. J Biol Chem. 2017;292:15287-15300 pubmed publisher..Collectively, these results suggest that the DTM is best described as a large cavity-forming protein assembly into which cytosolic PEX5 can enter to release its cargo. ..
- Chen E, Weng J, Chen Y, Wang S, Liu X, Huang W, et al. Phospho-Priming Confers Functionally Relevant Specificities for Rad53 Kinase Autophosphorylation. Biochemistry. 2017;56:5112-5124 pubmed publisher..Our results show that, while Rad53 can display active conformations under various conditions, simulation of in vivo regulatory conditions confers functionally relevant autophosphorylation. ..
- Booth W, Morris T, Mysona D, Shah M, Taylor L, Karlin T, et al. Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NH3 -dependent NAD+ synthetase. FEBS J. 2017;284:2425-2441 pubmed publisher..4.2.19 and NAD synthetase: EC188.8.131.52. Protein structures for spNadC, spNadC?69A , and spNadE are deposited into Protein Data Bank under the accession codes 5HUL, 5HUO & 5HUP, and 5HUH & 5HUJ, respectively. ..
- Schiller B, Chodankar R, Watson L, Stallcup M, Yamamoto K. Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes. Genome Biol. 2014;15:418 pubmed publisher..This approach may contribute to predictive models for GR activity and therapy. ..
- Maheshwari S, Miller M, O Meally R, Cole R, Amzel L, Gabelli S. Kinetic and structural analyses reveal residues in phosphoinositide 3-kinase ? that are critical for catalysis and substrate recognition. J Biol Chem. 2017;292:13541-13550 pubmed publisher..On the basis of these kinetic and structural analyses, we propose possible mechanistic roles of these critical residues in PI3K? catalysis. ..
- Jennings S, Chenevert M, Liu L, Mottamal M, Wojcik E, Huckaba T. Characterization of kinesin switch I mutations that cause hereditary spastic paraplegia. PLoS ONE. 2017;12:e0180353 pubmed publisher..This work provides mechanistic insight into the cause of HSP in patients with these mutations and points to future experiments to further dissect the root cause of this disease. ..
- Li Z, Zhang Y, Hedman A, Ames J, Sacks D. Calmodulin Lobes Facilitate Dimerization and Activation of Estrogen Receptor-Î±. J Biol Chem. 2017;292:4614-4622 pubmed publisher..In light of the critical role of ER-Î± in breast carcinoma, our data suggest that small molecules that selectively disrupt the interaction of ER-Î± with CaM may be useful in the therapy of breast carcinoma. ..
- Perlenfein T, Mehlhoff J, Murphy R. Insights into the mechanism of cystatin C oligomer and amyloid formation and its interaction with β-amyloid. J Biol Chem. 2017;292:11485-11498 pubmed publisher..This result illustrates an example where heterotypic interactions between pre-amyloid oligomers prevent the homotypic interactions that would lead to mature amyloid fibrils. ..
- Pontejo S, Murphy P. Two glycosaminoglycan-binding domains of the mouse cytomegalovirus-encoded chemokine MCK-2 are critical for oligomerization of the full-length protein. J Biol Chem. 2017;292:9613-9626 pubmed publisher..Thus, MCK-2 is an atypical viral chemokine consisting of a CC chemokine domain and a unique non-chemokine domain, both of which bind GAGs and are critical for GAG-dependent oligomerization of the full-length protein. ..
- Rizk M, Basler C, Guatelli J. Cooperation of the Ebola Virus Proteins VP40 and GP1,2 with BST2 To Activate NF-ÎºB Independently of Virus-Like Particle Trapping. J Virol. 2017;91: pubmed publisher..Better mechanistic understanding of these phenomena could provide targets for therapies that modulate the inflammatory response during Ebola virus disease. ..
- Arnott Z, Nozaki S, Monteiro D, Morgan H, Pearson A, Niki H, et al. The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ·AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan). Biochemistry. 2017;56:4931-4939 pubmed publisher..This both demonstrates that the PanDZ complex regulates pantothenate biosynthesis in a cellular context and validates the complex as a target for antibiotic development. ..
- Kshirsagar R, Ghodke I, Muniyappa K. Saccharomyces cerevisiae Red1 protein exhibits nonhomologous DNA end-joining activity and potentiates Hop1-promoted pairing of double-stranded DNA. J Biol Chem. 2017;292:13853-13866 pubmed publisher..Collectively, this study presents the first direct insights into Red1's mode of action and into the mechanism underlying its role in chromosome synapsis and recombination. ..
- Blair L, Nordhues B, Hill S, Scaglione K, O Leary J, Fontaine S, et al. Accelerated neurodegeneration through chaperone-mediated oligomerization of tau. J Clin Invest. 2013;123:4158-69 pubmed publisher..Strategies aimed at attenuating FKBP51 levels or its interaction with Hsp90 have the potential to be therapeutically relevant for AD and other tauopathies. ..
- KIM J, Nanfara M, Chodavarapu S, Jin K, Babu V, Ghazy M, et al. Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing. Nucleic Acids Res. 2017;45:3888-3905 pubmed publisher..In the octameric Hda-? clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. ..
- Liebsch F, Aurousseau M, Bethge T, McGuire H, Scolari S, Herrmann A, et al. Full-length cellular ?-secretase has a trimeric subunit stoichiometry, and its sulfur-rich transmembrane interaction site modulates cytosolic copper compartmentalization. J Biol Chem. 2017;292:13258-13270 pubmed publisher..In conclusion, therapeutic Alzheimer disease prevention strategies aimed at decreasing BACE1 protein levels should be regarded with caution, because adverse effects in copper homeostasis may occur. ..
- Novikov V, Mamaeva M, Aliasova A, Hazov M, Kasatova E, Shumilova S, et al. [THE SERUM LEVEL OF TOTAL AND OLIGOMERIC FRACTIONS OF SOLUBLE MOLECULES CD38 UNDER MALIGNANT TUMORS OF CERVIX AND UTERINE BODY]. Klin Lab Diagn. 2015;60:32-6 pubmed..On the whole, alterations in content of soluble molecules CD38 are associated with characteristics of tumor process that indicates at their monitoring significance under malignant neoplasms of uterus. ..
- Mandala V, Liao S, Kwon B, Hong M. Structural Basis for Asymmetric Conductance of the Influenza M2 Proton Channel Investigated by Solid-State NMR Spectroscopy. J Mol Biol. 2017;429:2192-2210 pubmed publisher..These results indicate that asymmetric conduction in WT M2 is due to W41 inhibition of C-terminal acid activation by H37. When Trp is replaced by Phe, protons can be transferred to H37 bidirectionally with distinct rate constants. ..
- Pliotas C, Grayer S, Ekkerman S, Chan A, Healy J, Marius P, et al. Adenosine Monophosphate Binding Stabilizes the KTN Domain of the Shewanella denitrificans Kef Potassium Efflux System. Biochemistry. 2017;56:4219-4234 pubmed publisher..We propose this interfacial binding site is itself stabilized, at least in part, by AMP binding...
- Sawicki A, Zhou S, Kwiatkowski K, Luo M, Willows R. 1-N-histidine phosphorylation of ChlD by the AAA+ ChlI2 stimulates magnesium chelatase activity in chlorophyll synthesis. Biochem J. 2017;474:2095-2105 pubmed publisher..The properties of ChlI2 compared with ChlI1 of Chlamydomonas and with ChlI of Oryza, shows that ChlI2 has a regulatory role in Chlamydomonas. ..
- Bassi R, Burgoyne J, DeNicola G, Rudyk O, DeSantis V, Charles R, et al. Redox-dependent dimerization of p38Î± mitogen-activated protein kinase with mitogen-activated protein kinase kinase 3. J Biol Chem. 2017;292:16161-16173 pubmed publisher..Our findings suggest that cysteine residues within p38Î± act as redox sensors that can dynamically regulate the association between p38 and MKK3. ..
- Schultz K, Lundquist T, Klug C. Lipopolysaccharide binding to the periplasmic protein LptA. Protein Sci. 2017;26:1517-1523 pubmed publisher..The results indicate that the entire protein is affected by LPS binding, the N-terminus unfolds in the presence of LPS, and a mutant LptA protein unable to form oligomers has an altered affinity for LPS. ..
- Waksman G. Structural and Molecular Biology of a Protein-Polymerizing Nanomachine for Pilus Biogenesis. J Mol Biol. 2017;429:2654-2666 pubmed publisher..Comparison with other nanomachines polymerizing other types of biological units, such as nucleotides during DNA replication, provides some unifying principles as to how multidomain proteins assemble biological polymers. ..
- Decarreau J, Wagenbach M, Lynch E, Halpern A, Vaughan J, KOLLMAN J, et al. The tetrameric kinesin Kif25 suppresses pre-mitotic centrosome separation to establish proper spindleÂ orientation. Nat Cell Biol. 2017;19:384-390 pubmed publisher..The activity of Kif25 during interphase is required to maintain a centred nucleus to ensure the spindle is stably oriented at the onset ofÂ mitosis. ..
- Wei P, Sun F, Zuo L, Qu J, Chen P, Xu L, et al. Critical residues and motifs for homodimerization of the first transmembrane domain of the plasma membrane glycoprotein CD36. J Biol Chem. 2017;292:8683-8693 pubmed publisher..Overall, this work provides a structural basis for understanding the role of TM association in regulating signal transduction via CD36. ..
- Alberga D, Trisciuzzi D, Lattanzi G, Bennett J, Verkman A, Mangiatordi G, et al. Comparative molecular dynamics study of neuromyelitis optica-immunoglobulin G binding to aquaporin-4 extracellular domains. Biochim Biophys Acta Biomembr. 2017;1859:1326-1334 pubmed publisher..Analysis of individual mutations suggested specific hydrogen bonding and other molecular interactions involved in AQP4-IgG binding to AQP4. ..
- Senger M, Stripp S, Soboh B. Proteolytic cleavage orchestrates cofactor insertion and protein assembly in [NiFe]-hydrogenase biosynthesis. J Biol Chem. 2017;292:11670-11681 pubmed publisher..Here, cleavage temporally orchestrates cofactor insertion and protein assembly and ensures that only cofactor-containing protein can continue along the assembly line toward functional [NiFe]-hydrogenase. ..
- Gupta K, Sharp R, Yuan J, Li H, Van Duyne G. Coiled-coil interactions mediate serine integrase directionality. Nucleic Acids Res. 2017;45:7339-7353 pubmed publisher..Together, the data provide a molecular basis for understanding serine integrase directionality. ..
- Fávero Retto M, Guerreiro L, Pessanha C, Palmieri L, Lima L. Polymorphic distribution of proteins in solution by mass spectrometry: The analysis of insulin analogues. Biologicals. 2017;45:69-77 pubmed publisher..The easiness of the technique provides further motivation for its application in the characterization of both raw and formulated protein biopharmaceuticals in routine and comparability exercises. ..
- Uchida T, Kobayashi N, Muneta S, Ishimori K. The Iron Chaperone Protein CyaY from Vibrio cholerae Is a Heme-Binding Protein. Biochemistry. 2017;56:2425-2434 pubmed publisher..Accordingly, the presence of excess heme in cells would lead to modulation of Fe-S cluster or heme biosynthesis. This report provides the first description of heme dependence of iron transport by CyaY. ..
- Akbal Delibas B, Haspel N. A conservation and biophysics guided stochastic approach to refining docked multimeric proteins. BMC Struct Biol. 2013;13 Suppl 1:S7 pubmed publisher..We aim to incorporate our refinement method in a larger framework which also enables docking of multimeric complexes given only monomeric structures. ..
- Zhang Y, Boxberger K, Hagenbuch B. Organic anion transporting polypeptide 1B3 can form homo- and hetero-oligomers. PLoS ONE. 2017;12:e0180257 pubmed publisher..These findings demonstrate that OATP1B3 can form homo- and hetero-oligomers and suggest a potential co-regulation of the involved transporters. ..