Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-Sm Abs recognize Sm core proteins B'/B, D, E, F, and G, shared by U1, U2, U4-6, and U5 small nuclear ribonucleoproteins (snRNPs), while anti-nuclear ribonucleoprotein Ag (nRNP) Abs recognize the U1 RNP-specific 70K, A, and C proteins. However, although the autoimmune response to U1 snRNPs involves all components of the particle, not all are recognized equally. For example, all human anti-nRNP sera contain Abs against native U1-C, in contrast to their absence in MRL/lpr mice. In this study, autoantibody recognition of native U1 snRNPs was investigated by dissociating the particle into four components (U1-70K, U1-A, U1-C, and the Sm core particle) using 1 M MgCl2 or ribonuclease treatment. As expected, human anti-Sm and MRL/lpr sera immunoprecipitated only the Sm core proteins, and human anti-nRNP/Sm sera immunoprecipitated the Sm core proteins plus U1-C under both conditions. However, although human anti-nRNP sera immunoprecipitated U1-C when U1 snRNPs were dissociated before Ab binding, they unexpectedly immunoprecipitated the Sm core proteins when Abs were bound before dissociation. This apparent paradox was explained by the stabilizing effects of anti-nRNP sera on interactions of U1-C with the Sm core particle. All human anti-nRNP sera contained high levels of autoantibodies that prevent dissociation of U1-C from the U1 snRNP. These Abs were absent in MRL/lpr mice. Human autoimmune sera may prevent dissociation by recognizing the quaternary structure of the U1-C-Sm core protein complex or by altering its conformation. Stabilization of U1 snRNPs by autoantibodies could influence Ag processing and presentation, possibly with important effects on the development of autoimmunity to U1 snRNPs.
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PMID:Human anti-nuclear ribonucleoprotein antigen autoimmune sera contain a novel subset of autoantibodies that stabilizes the molecular interaction of U1RNP-C protein with the Sm core proteins. 914 22

During apoptosis, the U1-70K protein, a component of the spliceosomal U1 snRNP complex, is specifically cleaved by the enzyme caspase-3, converting it into a C-terminally truncated 40-kDa fragment. In this study, we show that the 40-kDa U1-70K fragment is still associated with the complete U1 snRNP complex, and that no obvious modifications occur with the U1 snRNP associated proteins U1A, U1C and Sm-B/B'. Furthermore, it is described for the first time that the U1 snRNA molecule, which is the backbone of the U1 snRNP complex, is modified during apoptosis by the specific removal of the first 5 - 6 nucleotides including the 2,2, 7-trimethylguanosine (TMG) cap. The observations that U1 snRNA cleavage is very specific (no such modifications were detected for the other U snRNAs tested) and that U1 snRNA cleavage is markedly inhibited in the presence of caspase inhibitors, indicate that an apoptotically activated ribonuclease is responsible for the specific modification of U1 snRNA during apoptosis.
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PMID:The fate of U1 snRNP during anti-Fas induced apoptosis: specific cleavage of the U1 snRNA molecule. 1071 22

The Poisson-Boltzmann (PB) equation is widely used for modeling solvation effects. The computational cost of PB has restricted its applications largely to single-conformation calculations. The generalized Born (GB) model provides an approximation at substantially reduced cost. Currently the best GB methods reproduce PB results for electrostatic solvation energies with errors at ~5 kcal/mol. When two proteins form a complex, the net electrostatic contributions to the binding free energy are typically of the order of 5 to 10 kcal/mol. Similarly, the net contributions of individual residues to protein folding free energy are < 5 kcal/mol. Clearly in these applications the accuracy of current GB methods is insufficient. Here we present a simple scaling scheme that allows our GB method, GBr6, to reproduce PB results for binding, folding, and transfer free energies with high accuracy. From an ensemble of conformations sampled from molecular dynamics simulations, five were judiciously selected for PB calculations. These PB results were used for scaling GBr6. Tests on the binding free energies of the barnase-barstar, GTPase-WASp, and U1A-U1hpII complexes and on the folding free energy of FKBP show that the effects of point mutations calculated by scaled GBr6 are accurate to within 0.3 kcal/mol of PB results. Similar accuracy was also achieved for the free energies of transfer for ribonuclease Sa and insulin from the crystalline phase to the solution phase at various pH's. This method makes it possible to thoroughly sample the transient-complex ensemble in predicting protein binding rate constants and to incorporate conformational sampling in electrostatic modeling (such as done in the MM-GBSA approach) without loss of accuracy.
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PMID:Accurate Calculations of Binding, Folding, and Transfer Free Energies by a Scaled Generalized Born Method. 2346 99