Ya-Yue Van

Publications (2)8.2 Total impact

• Article: Utilization of Protein Intrinsic Disorder Knowledge in Structural Proteomics.

  Christopher J Oldfield, Bin Xue, Ya-Yue Van, Eldon L Ulrich, John L Markley, A Keith Dunker, Vladimir N Uversky
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  ABSTRACT: Intrinsically disordered proteins (IDPs) and proteins with long disordered regions are highly abundant in various proteomes. Despite their lack of well-defined ordered structure, these proteins and regions are frequently involved in crucial biological processes. Although in recent years these proteins have attracted the attention of many researchers, IDPs represent a significant challenge for structural characterization since these proteins can impact many of the processes in the structure determination pipeline. Here we investigate the effects of IDPs on the structure determination process and the utility of disorder prediction in selecting and improving proteins for structural characterization. Examination of the extent of intrinsic disorder in existing crystal structures found that relatively few protein crystal structures contain extensive regions of intrinsic disorder. Although intrinsic disorder is not the only cause of crystallization failures and many structured proteins cannot be crystallized, filtering out highly disordered proteins from structure-determination target lists is still likely to be cost effective. Therefore it is desirable to avoid highly disordered proteins from structure-determination target lists and we show that disorder prediction can be applied effectively to enrich structure determination pipelines with proteins more likely to yield crystal structures. For structural investigation of specific proteins, disorder prediction can be used to improve targets for structure determination. Finally, a framework for considering intrinsic disorder in the structure determination pipeline is proposed.
  Biochimica et Biophysica Acta 12/2012; · 4.66 Impact Factor
• Article: Protein intrinsic disorder and induced pluripotent stem cells.

  Bin Xue, Christopher J Oldfield, Ya-Yue Van, A Keith Dunker, Vladimir N Uversky
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  ABSTRACT: Induced pluripotent stem (iPS) cells can be obtained from terminally differentiated somatic cells by overexpression of defined sets of reprogramming transcription factors. These protein sets have been called the Yamanaka factors, namely Sox2, Oct3/4 (Pou5f1), Klf4, and c-Myc, and the Thomson factors, namely Sox2, Oct3, Lin28, and Nanog. Other sets of proteins, while not essential for the formation of iPS cells, are important for improving the efficiency of the induction and still other sets of proteins are important as markers for embryonic stem cells. Structural information about most of these important proteins is very sparse. Our bioinformatics analysis herein reveals that these reprogramming factors and most of the efficiency-improving and embryonic stem cell markers are highly enriched in intrinsic disorder. As is typical for transcription factors, these proteins are modular. Specific sites for interaction with other proteins and DNA are dispersed in the long regions of intrinsic disorder. These highly dynamic interaction sites are evidently responsible for the delicate interplay among various molecules. The bioinformatics analysis given herein should facilitate the investigation of the roles and organization of these modular interaction sites, thereby helping to shed further light on the pathways that underlie the mechanism(s) by which terminally differentiated cells are converted to iPS cells.
  Molecular BioSystems 07/2011; 8(1):134-50. · 3.53 Impact Factor