Solution structure and function of YndB, an AHSA1 protein from Bacillus subtilis

Authors

  • Jaime L. Stark,

    1. Department of Chemistry, University of Nebraska Lincoln, Lincoln, Nebraska 68588-0304
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    • Jaime L. Stark and Kelly A. Mercier contributed equally to this work.

  • Kelly A. Mercier,

    1. Department of Chemistry, University of Nebraska Lincoln, Lincoln, Nebraska 68588-0304
    2. Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Durham, North Carolina 27709
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    • Jaime L. Stark and Kelly A. Mercier contributed equally to this work.

  • Geoffrey A. Mueller,

    1. Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Durham, North Carolina 27709
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  • Thomas B. Acton,

    1. Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854
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  • Rong Xiao,

    1. Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854
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  • Gaetano T. Montelione,

    1. Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854
    2. Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 09954
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  • Robert Powers

    Corresponding author
    1. Department of Chemistry, University of Nebraska Lincoln, Lincoln, Nebraska 68588-0304
    • Department of Chemistry, 722 Hamilton Hall, University of Nebraska-Lincoln, Lincoln, NE 68588-0304
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  • The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases.

Abstract

The solution structure of the Bacillus subtilis protein YndB has been solved using NMR to investigate proposed biological functions. The YndB structure exhibits the helix-grip fold, which consists of a β-sheet with two small and one long α-helix, forming a hydrophobic cavity that preferentially binds lipid-like molecules. Sequence and structure comparisons with proteins from eukaryotes, prokaryotes, and archaea suggest that YndB is very similar to the eukaryote protein Aha1, which binds to the middle domain of Hsp90 and induces ATPase activity. On the basis of these similarities, YndB has been classified as a member of the activator of Hsp90 ATPase homolog 1-like protein (AHSA1) family with a function that appears to be related to stress response. An in silico screen of a compound library of ∼18,500 lipids was used to identify classes of lipids that preferentially bind YndB. The in silico screen identified, in order of affinity, the chalcone/hydroxychalcone, flavanone, and flavone/flavonol classes of lipids, which was further verified by 2D 1H-15N HSQC NMR titration experiments with trans-chalcone, flavanone, flavone, and flavonol. All of these compounds are typically found in plants as precursors to various flavonoid antibiotics and signaling molecules. The sum of the data suggests an involvement of YndB with the stress response of B. subtilis to chalcone-like flavonoids released by plants due to a pathogen infection. The observed binding of chalcone-like molecules by YndB is likely related to thesymbiotic relationship between B. subtilis and plants. Proteins 2010. © 2010 Wiley-Liss, Inc.

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