84 research outputs found
Atp11p and Atp12p are chaperones for F1-ATPase biogenesis in mitochondria
AbstractThe bioenergetic needs of aerobic cells are met principally through the action of the F1F0 ATP synthase, which catalyzes ATP synthesis during oxidative phosphorylation. The catalytic unit of the enzyme (F1) is a multimeric protein of the subunit composition α3β3γδΡ. Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial α and β subunits into the F1 oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. Comprehensive knowledge of Atp11p and Atp12p activities in mitochondria bears relevance to human physiology and disease as these chaperone actions are now known to exist in mitochondria of human cells
Multidimensional mutual information methods for the analysis of covariation in multiple sequence alignments
Several methods are available for the detection of covarying positions from a
multiple sequence alignment (MSA). If the MSA contains a large number of
sequences, information about the proximities between residues derived from
covariation maps can be sufficient to predict a protein fold. If the structure
is already known, information on the covarying positions can be valuable to
understand the protein mechanism.
In this study we have sought to determine whether a multivariate extension of
traditional mutual information (MI) can be an additional tool to study
covariation. The performance of two multidimensional MI (mdMI) methods,
designed to remove the effect of ternary/quaternary interdependencies, was
tested with a set of 9 MSAs each containing <400 sequences, and was shown to be
comparable to that of methods based on maximum entropy/pseudolikelyhood
statistical models of protein sequences. However, while all the methods tested
detected a similar number of covarying pairs among the residues separated by <
8 {\AA} in the reference X-ray structures, there was on average less than 65%
overlap between the top scoring pairs detected by methods that are based on
different principles.
We have also attempted to identify whether the difference in performance
among methods is due to different efficiency in removing covariation
originating from chains of structural contacts. We found that the reason why
methods that derive partial correlation between the columns of a MSA provide a
better recognition of close contacts is not because they remove chaining
effects, but because they filter out the correlation between distant residues
that originates from general fitness constraints. In contrast we found that
true chaining effects are expression of real physical perturbations that
propagate inside proteins, and therefore are not removed by the derivation of
partial correlation between variables.Comment: 21 pages, 4 figures, 1 table, supporting information containing 2
additional figures is included at the end of the manuscrip
Cloning and Sequence Analysis of the Structural Gene for the bc 1 - Type Rieske Iron-Sulfur Protein from Thermus thermophilus HB8
The structural gene encoding the Rieske iron-sulfur protein from Thermus thermophilus HB8 has been cloned and sequenced. The gene encodes a protein of 209 amino acids that begins with a hydrophilic N-terminus followed by a stretch of 21 hydrophobic amino acids that could serve as a transmembrane helix. The remainder of the protein has a hydrophobicity pattern typical of a water-soluble protein. A phylogenetic analysis of 26 Rieske proteins that are part of bc 1 or b 6 f complexes shows that they fall into three major groups: eubacterial and mitochondrial, cyanobacterial and plastid, and five highly divergent outliers, including that of Thermus . Although the overall homology with other Rieske proteins is very low, the C-terminal half of the Thermus protein contains the signature sequence CTHLGC-(13X)-CPCH that most likely provides the ligands of the [2Fe-2S] cluster. It is proposed that this region of the protein represents a small domain that folds independently and that the encoding DNA sequence may have been transferred during evolution to several unrelated genes to provide the cluster attachment site to proteins of different origin. The role of individual residues in this domain of the Thermus protein is discussed vis-a-vis the three-dimensional structure of the bovine protein (Iwata et al ., 1996 Structure 4 , 567β579).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44801/1/10863_2004_Article_409077.pd
Understanding the information needs of women with rheumatoid arthritis concerning pregnancy, post-natal care and early parenting: A mixed-methods study
Β© 2015 Ackerman et al. Background: Although women with rheumatoid arthritis (RA) face a number of challenges in negotiating the journey to parenthood, no studies have explored the information needs of women with RA in relation to their childbearing years. This study aimed to determine the need for (and preferred mode/s of delivery of) information regarding pregnancy, post-natal care and early parenting among women with RA. Methods: Interviews and focus groups were conducted with 27 women with RA who were pregnant in the last 5 years, currently pregnant or planning pregnancy. Verbatim transcripts were analysed using both inductive and deductive approaches. Two validated instruments were used to quantify information needs and preferences: the Educational Needs Assessment Tool (ENAT, range 0-156, higher scores indicate higher educational needs) and the Autonomy Preference Index (API, range 0-100, higher scores indicate stronger preferences). Results: Lack of information about medication safety, access to physical/emotional support services and practical strategies for coping with daily challenges related to parenting were the most prominent of the six key themes identified. Rheumatologists were the primary source for information regarding treatment decisions while arthritis consumer organisations were perceived as critical 'resource hubs'. There was strong preference for information delivered electronically, especially among rural participants. Quantitative outcomes supported the qualitative findings; on average, participants reported high educational needs (mean ENAT score 97.2, SD 30.8) and API scores indicated that desire for information (mean 89.8, SD 5.6) was greater than the need for involvement in treatment decision-making (mean 68.4, SD 8.2). Conclusions: Many women with RA struggle to find adequate information on pregnancy planning, pregnancy and early parenting in relation to their chronic condition, and there is a clear need to develop accessible information that is consumer-focused and evidence-based. Although most participants trusted their rheumatologist as their primary information source, there was consistent demand for more information, particularly regarding the safety of RA medications during pregnancy and breastfeeding, and the importance of learning from other women's personal experiences was strongly emphasised
The state of the Martian climate
60Β°N was +2.0Β°C, relative to the 1981β2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2Β°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications
Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (nβ=β1078) and Hispanic (nβ=β242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13--blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test
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This phase 1 study showed the feasibility of combining anti-HIV bnAbs targeting different sites on the HIV envelope in people living without HIV. It also showed that the dual-antibody and triple-antibody combinations were as effective as the individual antibodies at neutralisation, thus justifying a combination approach going forward for additional monoclonal antibody studies for HIV prevention. The fact that modelling predicted the combination neutralisation titre on the basis of the single antibody titres will be valuable for future trial design of different antibody combinations
The Contribution of Coevolving Residues to the Stability of KDO8P Synthase
The evolutionary tree of 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase (KDO8PS), a bacterial enzyme that catalyzes a key step in the biosynthesis of bacterial endotoxin, is evenly divided between metal and non-metal forms, both having similar structures, but diverging in various degrees in amino acid sequence. Mutagenesis, crystallographic and computational studies have established that only a few residues determine whether or not KDO8PS requires a metal for function. The remaining divergence in the amino acid sequence of KDO8PSs is apparently unrelated to the underlying catalytic mechanism.The multiple alignment of all known KDO8PS sequences reveals that several residue pairs coevolved, an indication of their possible linkage to a structural constraint. In this study we investigated by computational means the contribution of coevolving residues to the stability of KDO8PS. We found that about 1/4 of all strongly coevolving pairs probably originated from cycles of mutation (decreasing stability) and suppression (restoring it), while the remaining pairs are best explained by a succession of neutral or nearly neutral covarions.Both sequence conservation and coevolution are involved in the preservation of the core structure of KDO8PS, but the contribution of coevolving residues is, in proportion, smaller. This is because small stability gains or losses associated with selection of certain residues in some regions of the stability landscape of KDO8PS are easily offset by a large number of possible changes in other regions. While this effect increases the tolerance of KDO8PS to deleterious mutations, it also decreases the probability that specific pairs of residues could have a strong contribution to the thermodynamic stability of the protein
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