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NMR and X-ray structures of the putative sterol carrier protein 2 from Thermus thermophilus HB8 show conformational changes

  • Published:
Journal of Structural and Functional Genomics

Abstract

Sterol carrier protein 2 (SCP-2), also known as nonspecific lipid transfer protein, is a ubiquitous intracellular ~13 kDa protein found in mammals, insects, plants, archaea, and bacteria. Vertebrate SCP-2 has been implicated in a wide range of lipid-related functions in vitro, although its actual physiological role is still unknown. Tunnels in the protein serve as fatty acid binding vehicles. Here we report the first putative SCP-2 structure from a bacterium: specifically, the NMR and X-ray structures of the TTHA0401 protein (also designated as TT1886) from the extremely thermophilic bacterium Thermus thermophilus. The NMR structure and the two chain structures (chain A and chain B) of the asymmetric crystallographic unit (space group (P212121)) revealed an internal cavity. However, this cavity is open to the outside, forming a tunnel, in only one of those structures (chain A, X-ray). The location of this tunnel is different from the one found in other SCP-2 proteins, and inaccessible cavities have not been seen before in SCP structures. We present evidence that at physiological concentrations, TTHA0401 likely exists as a monomer in equilibrium between open and closed conformations. This equilibrium is influenced by temperature-dependent dynamics, and is likely to be very different at the high temperatures preferred by this hyperthermophilic bacterium. Alternatively, another protein binding to TTHA0401 may induce a conformational change, which would constitute an intriguing metabolic regulation method in bacteria.

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Abbreviations

SCP:

Sterol carrier protein

NOE:

Nuclear overhauser effect

PDB:

Protein data bank

RCSB:

Research collaboratory for structural bioinformatics (http://www.rcsb.org)

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Acknowledgments

The authors would like to thank the following persons: Tadashi Tomizawa, Makoto Inoue, Masaomi Ikari, Eiko Seki, Yasuko Tomo, Takayoshi Matsuda, Masaaki Aoki, Yukoko Fujikura, Takashi Yabuki, Natsuko Matsuda, Yoko Motoda, Yuki Kamewari-Hayami, Hideaki Tanaka, Miki Idaka, Kazushiga Katsura, Tomomi Uchikubo-Kamo, Machiko Yamaguchi-Hirafuji, Akiko Urushibata, Chie Takemoto, and Yoshitaka Bessho. For stimulating discussions, Geoffrey B. Jameson (Massey University, New Zealand) deserves special mention. This work was supported by the RIKEN Structural Genomics/Proteomics Initiative (RSGI), the National Project on Protein Structural and Functional Analyses, Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan

    Alexander K. Goroncy, Kazutaka Murayama, Mikako Shirouzu, Takanori Kigawa & Shigeyuki Yokoyama

  2. Tohoku University Biomedical Engineering Research Organization, Sendai, 980-8575, Japan

    Kazutaka Murayama

  3. RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo, 679-5148, Japan

    Seiki Kuramitsu

  4. Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan

    Seiki Kuramitsu

  5. Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Japan

    Takanori Kigawa

  6. Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan

    Shigeyuki Yokoyama

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  1. Alexander K. Goroncy
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  2. Kazutaka Murayama
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  6. Shigeyuki Yokoyama
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Correspondence to Shigeyuki Yokoyama.

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Goroncy, A.K., Murayama, K., Shirouzu, M. et al. NMR and X-ray structures of the putative sterol carrier protein 2 from Thermus thermophilus HB8 show conformational changes. J Struct Funct Genomics 11, 247–256 (2010). https://doi.org/10.1007/s10969-010-9096-5

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  • DOI: https://doi.org/10.1007/s10969-010-9096-5

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