Bin Xue

University of South Florida, Tampa, FL, United States

Are you Bin Xue?

Claim your profile

Publications (12)35.63 Total impact

  • Source
    [show abstract] [hide abstract]
    ABSTRACT: IDPs function without relying on three-dimensional structures. No clear rationale for such a behavior is available yet. PreSMos are transient secondary structures observed in the target-free IDPs and serve as the target-binding "active" motifs in IDPs. Prolines are frequently found in the flanking regions of PreSMos. Contribution of prolines to the conformational stability of the helical PreSMos in IDPs is investigated. MD simulations are performed for several IDP segments containing a helical PreSMo and the flanking prolines. To measure the influence of flanking-prolines on the structural content of a helical PreSMo calculations were done for wild type as well as for mutant segments with Pro■Asp, His, Lys, or Ala. The change in the helicity due to removal of a proline was measured both for the PreSMo region and for the flanking regions. The α-helical content in ~70% of the helical PreSMos at the early stage of simulation decreases due to replacement of an N-terminal flanking proline by other residues whereas the helix content in nearly all PreSMos increases when the same replacements occur at the C-terminal flanking region. The helix destabilizing/terminating role of the C-terminal flanking prolines is more pronounced than the helix promoting effect of the N-terminal flanking prolines. General Significance This work represents a novel example demonstrating that a proline is encoded in an IDP with a defined purpose. The helical PreSMos presage their target-bound conformations. As they most likely mediate IDP-target binding via conformational selection their helical content can be an important feature for IDP function.
    Biochimica et Biophysica Acta 11/2013; · 4.66 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Intrinsically disordered proteins (IDPs) and proteins with long intrinsically disordered protein regions (IDPRs) lack ordered structure but are involved in a multitude of biological processes, where they often serve as major regulators and controllers of various functions of their binding partners. Furthermore, IDPs/IDPRs are often related to the pathogenesis of various diseases, including cancer. Intrinsic disorder confers multiple functional advantages to its carriers. As a result, due to their functional versatility and structural plasticity, IDPs and IDPRs are common in various proteomes, including proteomes of different pathological organisms. Viruses are "well-educated" users of various aspects of intrinsic disorder for their advantage. These small but highly efficient invaders broadly use intrinsic disorder to overrun the host organism's defense system, as well as to seize and overrun host systems and pathways forcing them to work for the virus needs, to ensure accommodation of viruses to their variable and often hostile habitats, and to promote and support the economic usage of the viral genetic material. Human papillomaviruses (HPVs), with their tiny proteomes (the entire HPV genome includes just eight open reading frames), intricate life cycle, and ability to either cause benign papillomas/warts or promote the development of carcinomas of the genital tract, head and neck and epidermis, attracted considerable attention of researchers. This review analyzes the plentitude and demeanor of intrinsic disorder in proteins from HPVs and their cellular targets.
    Current pharmaceutical design 05/2013; · 4.41 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: https://is.landesbioscience.com/article/25724/full_text/#load/info/all The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members of the version 23.0 Pfam seed database. To include the maximum information available for proteins that remain unfolded in solution, we employ the 10 linearly independent Kidera factors1–3 for the amino acids, combined with PONDR4 predictions of disorder tendency, to transform the sequences of these Pfam members into an 11 column matrix where the number of rows is the length of each Pfam region. Cluster analyses of the set of all regions, including those that are folded, show 6 groupings of domains. Cluster analyses of domains with mean VSL2b scores greater than 0.5 (half predicted disorder or more) show at least 3 separated groups. It is hypothesized that grouping sets into shorter sequences with more uniform length will reveal more information about intrinsic disorder and lead to more finely structured and perhaps more accurate predictions. HMMs could be trained to include this information.
    Intrinsically Disordered Proteins. 04/2013; 1(1):e25724.
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Intrinsically disordered proteins (IDPs) are a relatively recently defined class of proteins which, under native conditions, lack a unique tertiary structure whilst maintaining essential biological functions. Functional classification of IDPs have implicated such proteins as being involved in various physiological processes including transcription and translation regulation, signal transduction and protein modification. Actinidia DRM1 (Ade DORMANCY ASSOCIATED GENE 1), represents a robust dormancy marker whose mRNA transcript expression exhibits a strong inverse correlation with the onset of growth following periods of physiological dormancy. Bioinformatic analyses suggest that DRM1 is plant specific and highly conserved at both the nucleotide and protein levels. It is predicted to be an intrinsically disordered protein with two distinct highly conserved domains. Several Actinidia DRM1 homologues, which align into two distinct Actinidia-specific families, Type I and Type II, have been identified. No candidates for the Arabidopsis DRM1-Homologue (AtDRM2) an additional family member, has been identified in Actinidia.
    PLoS ONE 01/2013; 8(3):e57354. · 3.73 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: In proteins, all amino acid residues are susceptible to oxidation by various reactive oxygen species (ROS), with methionine and cysteine residues being particularly sensitive to oxidation. Methionine oxidation is known to lead to destabilization and inactivation of proteins, and oxidatively modified proteins can accumulate during aging, oxidative stress, and in various age-related diseases. Although the efficiency of a given methionine oxidation can depend on its solvent accessibility (evaluated from a protein structure as the accessible surface area of the corresponding methionine residue), many experimental results on oxidation rate and oxidation sites cannot be unequivocally explained by the methionine solvent accessible surface area alone. In order to explore other possible mechanisms, we analyzed a set of seventy-one oxidized methionines contained in thirty-one proteins by various bioinformatics tools. In which, 41% of the methionines are exposed, 15% are buried but with various degree of flexibility, and the rest 44% are buried and structured. Buried but highly flexible methionines can be oxidized. Buried and less flexible methionines can acquire additional local structural flexibility from flanking regions to facilitate the oxidation. Oxidation of buried and structured methionine can also be promoted by the oxidation of neighboring methionine that is more exposed and/or flexible. Our data are consistent with the hypothesis that protein structural flexibility represents another important factor favoring the oxidation process.
    Protein and Peptide Letters 04/2012; 19(6):688-97. · 1.99 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Protein structural class prediction is one of the challenging problems in bioinformatics. Previous methods directly based on the similarity of amino acid (AA) sequences have been shown to be insufficient for low-similarity protein data-sets. To improve the prediction accuracy for such low-similarity proteins, different methods have been recently proposed that explore the novel feature sets based on predicted secondary structure propensities. In this paper, we focus on protein structural class prediction using combinations of the novel features including secondary structure propensities as well as functional domain (FD) features extracted from the InterPro signature database. Our comprehensive experimental results based on several benchmark data-sets have shown that the integration of new FD features substantially improves the accuracy of structural class prediction for low-similarity proteins as they capture meaningful relationships among AA residues that are far away in protein sequence. The proposed prediction method has also been tested to predict structural classes for partially disordered proteins with the reasonable prediction accuracy, which is a more difficult problem comparing to structural class prediction for commonly used benchmark data-sets and has never been done before to the best of our knowledge. In addition, to avoid overfitting with a large number of features, feature selection is applied to select discriminating features that contribute to achieve high prediction accuracy. The selected features have been shown to achieve stable prediction performance across different benchmark data-sets.
    Journal of biomolecular structure & dynamics 04/2012; 29(6):623-33. · 4.99 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Voltage-gated potassium (Kv) channels are tetrameric assemblies of transmembrane Kv proteins with cytosolic N- and C-termini. The N-terminal domain of Kv1 proteins binds to β-subunits, but the role of the C-terminus is less clear. Therefore, we studied the role of the C-terminus in regulating Kv1.5 channel and its interactions with Kvβ-subunits. When expressed in COS-7 cells, deletion of the C-terminal domain of Kv1.5 did not affect channel gating or kinetics. Coexpression of Kv1.5 with Kvβ3 increased current inactivation, whereas Kvβ2 caused a hyperpolarizing shift in the voltage dependence of current activation. Inclusion of NADPH in the patch pipette solution accelerated the inactivation of Kv1.5-Kvβ3 currents. In contrast, NADP(+) decreased the rate and the extent of Kvβ3-induced inactivation and reversed the hyperpolarizing shift in the voltage dependence of activation induced by Kvβ2. Currents generated by Kv1.5ΔC+Kvβ3 or Kv1.5ΔC+Kvβ2 complexes did not respond to changes in intracellular pyridine nucleotide concentration, indicating that the C-terminus is required for pyridine nucleotide-dependent interactions between Kvβ and Kv1.5. A glutathione-S-transferase (GST) fusion protein containing the C-terminal peptide of Kv1.5 did not bind to apoKvβ2, but displayed higher affinity for Kvβ2:NADPH than Kvβ2:NADP(+). The GST fusion protein also precipitated Kvβ proteins from mouse brain lysates. Pull-down experiments, structural analysis and electrophysiological data indicated that a specific region of the C-terminus (Arg543-Val583) is required for Kvβ binding. These results suggest that the C-terminal domain of Kv1.5 interacts with β-subunits and that this interaction is essential for the differential regulation of Kv currents by oxidized and reduced nucleotides.
    Pflügers Archiv - European Journal of Physiology 03/2012; 463(6):799-818. · 4.87 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The extracellular matrix is very well organized at the supramolecular and tissue levels and little is known on the potential role of intrinsic disorder in promoting its organization. We predicted the amount of disorder and identified disordered regions in the human extracellular proteome with established computational tools. The extracellular proteome is significantly enriched in proteins comprising more than 50% of disorder compared to the complete human proteome. The enrichment is mostly due to long disordered regions containing at least 100 consecutive disordered residues. The amount of intrinsic disorder is heterogeneous in the extracellular protein families, with the most disordered being collagens and the small integrin-binding ligand N-linked glycoproteins. Although most domains found in extracellular proteins are structured, the fibronectin III domains contain a variable amount of disordered residues (up to 92%). Binding sites for heparin and integrins are found in disordered sequences of extracellular proteins. Intrinsic disorder is evenly distributed in hubs and ends in the interaction network of extracellular proteins with their extracellular partners. In contrast, extracellular hubs are significantly enriched in disorder in the network of extracellular proteins with their extracellular, membrane and intracellular partners. Disorder could thus provide the structural plasticity required for the hubs to interact with membrane and intracellular proteins. Organization and assembly of the extracellular matrix, development of mineralized tissues and cell-matrix adhesion are the biological processes overrepresented in the most disordered extracellular proteins. Extracellular disorder is associated with binding to growth factors, glycosaminoglycans and integrins at the molecular level.
    Molecular BioSystems 12/2011; 7(12):3353-65. · 3.35 Impact Factor
  • 02/2011: pages 169-200;
  • 02/2011: pages 143-167;
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: We analysed the structural properties of protein regions containing arrays of perfect and nearly perfect tandem repeats. Naturally occurring proteins with perfect repeats are practically absent among the proteins with known 3D structures. The great majority of such regions in the Protein Data Bank are found in the proteins designed de novo. The abundance of natural structured proteins with tandem repeats is inversely correlated with the repeat perfection: the chance of finding natural structured proteins in the Protein Data Bank increases with a decrease in the level of repeat perfection. Prediction of intrinsic disorder within the tandem repeats in the SwissProt proteins supports the conclusion that the level of repeat perfection correlates with their tendency to be unstructured. This correlation is valid across the various species and subcellular localizations, although the level of disordered tandem repeats varies significantly between these datasets. On average, in prokaryotes, tandem repeats of cytoplasmic proteins were predicted to be the most structured, whereas in eukaryotes, the most structured portion of the repeats was found in the membrane proteins. Our study supports the hypothesis that, in general, the repeat perfection is a sign of recent evolutionary events rather than of exceptional structural and (or) functional importance of the repeat residues.
    FEBS Journal 06/2010; 277(12):2673-82. · 4.25 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Light chain amyloidoses arise from the overproduction and abnormal deposition of the immunoglobulin light chain in various organs. LEN is the variable domain of an immunoglobulin light chain originally isolated from the urine of a patient suffering from multiple myeloma, with no sign of renal dysfunction or amyloidosis. LEN was shown to form fibrils in vitro under mildly destabilizing conditions. In this work, we investigated the changes induced by methionine oxidation in the structural properties, conformational stability, and aggregation behavior of immunoglobulin light chain domain LEN. We established that LEN was well-protected from oxidation in its native state, but successful oxidation was achieved in the presence of 4 M GuHCl. Oxidation induced noticeable structural changes in LEN and destabilized this protein. The methionine-oxidized LEN preferred to form amorphous aggregates instead of fibrils. The results indicated that the LEN oxidation may play an important role in amorphous deposition of the protein, but not in its fibrillation.
    Biochemistry 08/2008; 47(33):8665-77. · 3.38 Impact Factor