Comprehensive large-scale assessment of intrinsic protein disorder

et al. 2016

104

In the last 2 decades it has become increasingly evident that a large number of proteins are either fully or partially disordered. Intrinsically disordered proteins lack a stable 3D structure, are ubiquitous and fulfill essential biological functions. Their conformational heterogeneity is encoded in their amino acid sequences, thereby allowing intrinsically disordered proteins or regions to be recognized based on properties of these sequences. The identification of disordered regions facilitates the functional annotation of proteins and is instrumental for delineating boundaries of protein domains amenable to structural determination with X-ray crystallization. This article discusses a comprehensive selection of databases and methods currently employed to disseminate experimental and putative annotations of disorder, predict disorder and identify regions involved in induced folding. It also provides a set of detailed instructions that should be followed to perform computational analysis of disorder.KEYWORDS disorder databases and metaservers; induced folding; intrinsic disorder; intrinsically disordered proteins; intrinsically disordered regions; prediction methods

Section: Running Disorder Predictionsmentioning

confidence: 93%

“…12,69,71,[76][77][78][79][80]. The availability of different types of predictors allows users to select various aspects of disorder prediction that are suitable to their current studies, and choose an appropriate predictor.…”

Section: Introductionmentioning

confidence: 99%

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

Lieutaud

Ferrón

et al. 2016

104

“…In addition, a positive correlation has been found between the increase of disorder content and the increase in the biological complexity during evolution. 63,65,[71][72][73][74][75] The microalgae O. tauri is the smallest and simplest photosynthetic . Although these 2 proteins show high overall sequence identity, the sequence similarity is low at their termini, where the IDRs are located.…”

Section: Resultsmentioning

confidence: 99%

“…Use of consensus for evaluation of intrinsic disorder is motivated by empirical observations that this approach usually increases the predictive performance compared to the use of a single predictor. [65][66][67] Potential disorder-based protein binding sites of query proteins (molecular recognition features, MoRFs) were identified by the ANCHOR algorithm. 68,69 This algorithm utilizes the pair-wise energy estimation approach originally used by IUPred 62,70 and acts on the hypothesis that long regions of disorder include localized potential binding sites which are not capable of folding on their own due to not being able to form enough favorable intrachain interactions, but can obtain the energy to stabilize via interaction with a globular protein partner.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the intrinsic disorder propensities of the RuBisCO activase enzyme from the motile and non-motile oceanic green microalgae

Sena

2016

Green oceanic microalgae are efficient converters of solar energy into the biomass via the photosynthesis process, with the first step of carbon fixation in the photosynthesis being controlled by the enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO), which is a large proteinaceous machine composed of large (L, 52 kDa) and small (S, 12 kDa) subunits arranged as a L 8 S 8 hexadecamer that catalyzes the formation of 2 phosphoglyceric acid molecules from one ribulose 1,5-bisphosphate (RuBP) molecule and one of carbon dioxide (CO 2 ) and that is considered as the most abundant protein on Earth. The catalytic efficiency of this protein is controlled by the RuBisCO activase (RCA) that interacts with RuBisCO and promotes the CO 2 entrance to the active site of RuBisCO by removing RuBP. One of the peculiar features of RCA is the presence of functional disordered tails that might play a role in RCA-RuBisCO interaction. Based on their ability to move, microalgae are grouped into 2 major class, motile and non-motile. Motile microalgae have an obvious advantage over their non-motile counterparts because of their ability to actively migrate within the water column to find the most optimal environmental conditions. We hypothesizes that the RCA could be functionally different in the non-motile and motile microalgae. To check this hypothesis, we conducted a comparative computational analysis of the RCAs from the representatives of the non-motile (Ostreococcus tauri) and motile (Tetraselmis sp. GSL018) green oceanic microalgae.

“…Use of consensus for evaluation of intrinsic disorder is motivated by empirical observations that this approach usually increases the predictive performance compared to the use of a single predictor. [30][31][32] We further characterized the disorder status of query proteins using the MobiDB database (http://mobidb. bio.unipd.it/), 33,34 that generates consensus disorder scores by aggregating the output from 10 predictors, such as 2 versions of IUPred, 29 PV2, 43 and ESpritz.…”

Section: Methodsmentioning

confidence: 99%

Understanding the roles of intrinsic disorder in subunits of hemoglobin and the disease process of sickle cell anemia

Fitzsimmons

Amin

2016

One of the common genetic disorders is sickle cell anemia, in which 2 recessive alleles must meet to allow for destruction and alteration in the morphology of red blood cells. This usually leads to loss of proper binding of oxygen to hemoglobin and curved, sickle-shaped erythrocytes. The mutation causing this disease occurs in the 6 th codon of the HBB gene encoding the hemoglobin subunit b (b-globin), a protein, serving as an integral part of the adult hemoglobin A (HbA), which is a heterotetramer of 2 a chains and 2 b chains that is responsible for binding to the oxygen in the blood. This mutation changes a charged glutamic acid to a hydrophobic valine residue and disrupts the tertiary structure and stability of the hemoglobin molecule. Since in the field of protein intrinsic disorder, charged and polar residues are typically considered as disorder promoting, in opposite to the order-promoting non-polar hydrophobic residues, in this study we attempted to answer a question if intrinsic disorder might have a role in the pathogenesis of sickle cell anemia. To this end, several disorder predictors were utilized to evaluate the presence of intrinsically disordered regions in all subunits of human hemoglobin: a, b, d, e, z, g1, and g2. Then, structural analysis was completed by using the SWISS-MODEL Repository to visualize the outputs of the disorder predictors. Finally, Uniprot STRING and D 2 P 2 were used to determine biochemical interactome and protein partners for each hemoglobin subunit along with analyzing their posttranslational modifications. All these properties were used to determine any differences between the 6 different types of subunits of hemoglobin and to correlate the mutation leading to sickle cell anemia with intrinsic disorder propensity.