Yawen Bai

National Cancer Institute (USA), 베서스다, Maryland, United States

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Publications (69)507.33 Total impact

  • Biophysical Society Annual Meeting 2015; 10/2015
  • Journal of biomolecular Structure & Dynamics 05/2015; 33(sup1):2-3. DOI:10.1080/07391102.2015.1032629 · 2.98 Impact Factor
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    ABSTRACT: The p53 tumor suppressor is a critical mediator of the cellular response to stress. The N-terminal transactivation domain of p53 makes protein interactions that promote its function as a transcription factor. Among those cofactors is the histone acetyltransferase p300, which both stabilizes p53 and promotes local chromatin unwinding. Here, we report the NMR solution structure of the Taz2 domain of p300 bound to the second transactivation subdomain of p53. In the complex, p53 forms an α-helix between residues 47-55 that interacts with the α1- α2- α3 face of Taz2. Mutational analysis indicated several residues in both p53 and Taz2 that are critical for stabilizing the interaction. Finally, further characterization of the complex by isothermal titration calorimetry revealed that complex formation is pH-dependent and releases a bound chloride ion. This study highlights differences in the structures of complexes formed by the two transactivation subdomains of p53 which may be broadly observed and play critical roles for p53 transcriptional activity.
    Biochemistry 03/2015; 54(11). DOI:10.1021/acs.biochem.5b00044 · 3.19 Impact Factor
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    ABSTRACT: Histone variant H2A.Z-containing nucleosomes exist at most eukaryotic promoters and play important roles in gene transcription and genome stability. The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. How SWR1 catalyzes the replacement reaction is largely unknown. Here, we determined the crystal structure of the N-terminal region (599-627) of the catalytic subunit Swr1, termed Swr1-Z domain, in complex with the H2A.Z-H2B dimer at 1.78 Å resolution. The Swr1-Z domain forms a 310 helix and an irregular chain. A conserved LxxLF motif in the Swr1-Z 310 helix specifically recognizes the αC helix of H2A.Z. Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.
    Molecular cell 02/2014; 53(3):498-505. DOI:10.1016/j.molcel.2014.01.010 · 14.46 Impact Factor
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    ABSTRACT: Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1-nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo.
    Proceedings of the National Academy of Sciences 11/2013; 110(48). DOI:10.1073/pnas.1314905110 · 9.81 Impact Factor
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    ABSTRACT: Comment on: Kato H, et al. Science 2013; 340:1110-3.
    Cell cycle (Georgetown, Tex.) 09/2013; 12(19). DOI:10.4161/cc.26353 · 5.01 Impact Factor
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    ABSTRACT: Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.
    Science 05/2013; 340(6136):1110-3. DOI:10.1126/science.1235532 · 31.48 Impact Factor
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    ABSTRACT: In eukaryotes, a variant of conventional histone H3 termed CenH3 epigenetically marks the centromere. The conserved CenH3 chaperone specifically recognizes CenH3 and is required for CenH3 deposition at the centromere. Recently, the structures of the chaperone/CenH3/H4 complexes have been determined for Homo sapiens (Hs) and the budding yeasts Saccharomyces cerevisiae (Sc) and Kluyveromyces lactis (Kl). Surprisingly, the three structures are very different, leading to different proposed structural bases for chaperone function. The question of which structural region of CenH3 provides the specificity determinant for the chaperone recognition is not fully answered. Here, we investigated these issues using solution NMR and site-directed mutagenesis. We discovered that, in contrast to previous findings, the structures of the Kl and Sc chaperone/CenH3/H4 complexes are actually very similar. This new finding reveals that both budding yeast and human chaperones use a similar structural region to block DNA from binding to the histones. Our mutational analyses further indicate that the N-terminal region of the CenH3 α2 helix is sufficient for specific recognition by the chaperone for both budding yeast and human. Thus, our studies have identified conserved structural bases of how the chaperones recognize CenH3 and perform the chaperone function.
    Journal of Molecular Biology 01/2013; 425:536-545. · 3.96 Impact Factor
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    ABSTRACT: In eukaryotes, a variant of conventional histone H3 termed CenH3 epigenetically marks the centromere. The conserved CenH3chaperone specifically recognizes CenH3 and is required for CenH3 deposition at the centromere. Recently, the structures of the chaperone/CenH3/H4 complexes have been determined for H. sapiens (Hs) andthe budding yeastsS. cerevisiae (Sc) and K. lactis (Kl). Surprisingly, the three structures arevery different, leading to different proposed structural bases for chaperone function.The question of which structural region of CenH3 providesthe specificity determinant for the chaperone recognition is not fully answered.Here, we investigated these issues usingsolution NMR and site-directed mutagenesis. We discovered that, in contrast to previous findings, the structures of the Kland Sc chaperone/CenH3/H4 complexes are actually very similar. This new finding reveals that both budding yeast and human chaperones use a similar structural region to block DNA from binding to the histones. Our mutational analyses further indicate that the N-terminal region of the CenH3α2 helix is sufficient for specific recognition by the chaperone for both budding yeast and human. Thus, our studies have identifiedconserved structural bases of how the chaperonesrecognize CenH3 and perform the chaperone function.
    Journal of Molecular Biology 11/2012; 425(3). DOI:10.1016/j.jmb.2012.11.021 · 3.96 Impact Factor
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    ABSTRACT: Histone tails and their posttranslational modifications play important roles in regulating the structure and dynamics of chromatin. For histone H4, the basic patch K(16)R(17)H(18)R(19) in the N-terminal tail modulates chromatin compaction and nucleosome sliding catalyzed by ATP-dependent ISWI chromatin remodeling enzymes while acetylation of H4 K16 affects both functions. The structural basis for the effects of this acetylation is unknown. Here, we investigated the conformation of histone tails in the nucleosome by solution NMR. We found that backbone amides of the N-terminal tails of histones H2A, H2B, and H3 are largely observable due to their conformational disorder. However, only residues 1-15 in H4 can be detected, indicating that residues 16-22 in the tails of both H4 histones fold onto the nucleosome core. Surprisingly, we found that K16Q mutation in H4, a mimic of K16 acetylation, leads to a structural disorder of the basic patch. Thus, our study suggests that the folded structure of the H4 basic patch in the nucleosome is important for chromatin compaction and nucleosome remodeling by ISWI enzymes while K16 acetylation affects both functions by causing structural disorder of the basic patch K(16)R(17)H(18)R(19).
    Journal of Molecular Biology 05/2012; 421(1):30-7. DOI:10.1016/j.jmb.2012.04.032 · 3.96 Impact Factor
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    ABSTRACT: Comment on: Zhou et al. Nature 2011; 47:234-237, Hu et al. Genes Dev 2011; 25:901-6 and Cho et al. Proc Natl Acad Sci USA 2011; 108:9367-71.
    Cell cycle (Georgetown, Tex.) 10/2011; 10(19):3217-8. DOI:10.4161/cc.10.19.17077 · 5.01 Impact Factor
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    Proceedings of the National Academy of Sciences 08/2011; 108(35):E596; author reply E597. DOI:10.1073/pnas.1109548108 · 9.81 Impact Factor
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    ABSTRACT: Chromatin structure and function are regulated by numerous proteins through specific binding to nucleosomes. The structural basis of many of these interactions is unknown, as in the case of the high mobility group nucleosomal (HMGN) protein family that regulates various chromatin functions, including transcription. Here, we report the architecture of the HMGN2-nucleosome complex determined by a combination of methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal DNA near the entry/exit point, "stapling" the histone core and the DNA. These results provide insight into how HMGNs regulate chromatin structure through interfering with the binding of linker histone H1 to the nucleosome as well as a structural basis of how phosphorylation induces dissociation of HMGNs from chromatin during mitosis. Importantly, our approach is generally applicable to the study of nucleosome-binding interactions in chromatin.
    Proceedings of the National Academy of Sciences 07/2011; 108(30):12283-8. DOI:10.1073/pnas.1105848108 · 9.81 Impact Factor
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    ABSTRACT: The centromere is a unique chromosomal locus that ensures accurate segregation of chromosomes during cell division by directing the assembly of a multiprotein complex, the kinetochore. The centromere is marked by a conserved variant of conventional histone H3 termed CenH3 or CENP-A (ref. 2). A conserved motif of CenH3, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions of CenH3 (refs 3, 4). The structural basis of this specification is of particular interest. Yeast Scm3 and human HJURP are conserved non-histone proteins that interact physically with the (CenH3-H4)(2) heterotetramer and are required for the deposition of CenH3 at centromeres in vivo. Here we have elucidated the structural basis for recognition of budding yeast (Saccharomyces cerevisiae) CenH3 (called Cse4) by Scm3. We solved the structure of the Cse4-binding domain (CBD) of Scm3 in complex with Cse4 and H4 in a single chain model. An α-helix and an irregular loop at the conserved amino terminus and a shorter α-helix at the carboxy terminus of Scm3(CBD) wraps around the Cse4-H4 dimer. Four Cse4-specific residues in the N-terminal region of helix 2 are sufficient for specific recognition by conserved and functionally important residues in the N-terminal helix of Scm3 through formation of a hydrophobic cluster. Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome.
    Nature 03/2011; 472(7342):234-7. DOI:10.1038/nature09854 · 42.35 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 02/2010; 30(5). DOI:10.1002/chin.199905296
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    ABSTRACT: The three-dimensional structures of macromolecules fluctuate over a wide range of time-scales. Separating the individual dynamic processes according to frequency is of importance in relating protein motions to biological function and stability. We present here a general NMR method for the specific characterization of microsecond motions at backbone positions in proteins even in the presence of other dynamics such as large-amplitude nanosecond motions and millisecond chemical exchange processes. The method is based on measurement of relaxation rates of four bilinear coherences and relies on the ability of strong continuous radio frequency fields to quench millisecond chemical exchange. The utility of the methodology is demonstrated and validated through two specific examples focusing on the thermo-stable proteins, ubiquitin and protein L, where it is found that small-amplitude microsecond dynamics are more pervasive than previously thought. Specifically, these motions are localized to alpha helices, loop regions, and regions along the rim of beta sheets in both of the proteins examined. A third example focuses on a 28 kDa ternary complex of the chaperone Chz1 and the histones H2A.Z/H2B, where it is established that pervasive microsecond motions are localized to a region of the chaperone that is important for stabilizing the complex. It is further shown that these motions can be well separated from extensive millisecond dynamics that are also present and that derive from exchange of Chz1 between bound and free states. The methodology is straightforward to implement, and data recorded at only a single static magnetic field are required.
    Journal of the American Chemical Society 11/2009; 131(44):16257-65. DOI:10.1021/ja906842s · 11.44 Impact Factor

Publication Stats

4k Citations
507.33 Total Impact Points

Institutions

  • 1999–2015
    • National Cancer Institute (USA)
      • • Laboratory of Biochemistry and Molecular Biology
      • • Chemical Biology Laboratory
      • • Center for Cancer Research
      베서스다, Maryland, United States
  • 2002–2012
    • National Institutes of Health
      • • Laboratory of Biochemistry and Molecular Biology
      • • Chemical Biology Laboratory
      Maryland, United States
  • 2006–2011
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2010
    • Philadelphia University
      Philadelphia, Pennsylvania, United States
  • 2008
    • The American Society for Biochemistry and Molecular Biology
      Maryland, United States
  • 2005–2007
    • University of Toronto
      • • Department of Biochemistry
      • • Department of Chemistry
      Toronto, Ontario, Canada
  • 2002–2006
    • Northern Inyo Hospital
      BIH, California, United States
  • 1996–1997
    • The Scripps Research Institute
      • Department of Cell and Molecular Biology
      لا هویا, California, United States
  • 1994
    • Union College
      • Chemistry
      Schenectady, New York, United States
  • 1993–1994
    • University of Pennsylvania
      • Department of Biochemistry and Biophysics
      Philadelphia, Pennsylvania, United States