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Crystal structure of a MARCKS peptide containing the calmodulin-binding domain in complex with Ca2+-calmodulin

Nature Structural & Molecular Biology volume 10, pages 226–231 (2003)Cite this article

Abstract

The calmodulin-binding domain of myristoylated alanine-rich C kinase substrate (MARCKS), which interacts with various targets including calmodulin, actin and membrane lipids, has been suggested to function as a crosstalk point among several signal transduction pathways. We present here the crystal structure at 2 Å resolution of a peptide consisting of the MARCKS calmodulin (CaM)-binding domain in complex with Ca2+-CaM. The domain assumes a flexible conformation, and the hydrophobic pocket of the calmodulin N-lobe, which is a common CaM-binding site observed in previously resolved Ca2+-CaM–target peptide complexes, is not involved in the interaction. The present structure presents a novel target-recognition mode of calmodulin and provides insight into the structural basis of the flexible interaction module of MARCKS.

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Figure 1: CaM-binding domain of MARCKS-related proteins.
Figure 2: Comparison of the complex with other CaM–target peptide complexes.
Figure 3: Titration of dansyl-CaM with the 19-residue MARCKS peptide.
Figure 4: Crystal structure of MARCKS peptide–CaM complex.

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Acknowledgements

We are grateful to M. Yamamoto and T. Kumasaka for X-ray diffraction data collection and data processing at beamline BL45XU-SAX. We thank O. de Montellano for providing the human CaM cDNA. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Japan Society for the Promotion of Science.

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Author notes

  1. Hiroaki Kato

    Present address: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan

  2. Mamoru Matsubara

    Present address: R&D Laboratories, Nippon Organon K.K., 1-5-90 Tomobuchi-cho, Osaka, 534-0016, Japan

Authors and Affiliations

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

    Emiko Yamauchi, Toru Nakatsu, Mamoru Matsubara, Hiroaki Kato & Hisaaki Taniguchi

  2. Institute for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan

    Emiko Yamauchi & Hisaaki Taniguchi

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Correspondence to Hisaaki Taniguchi.

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Yamauchi, E., Nakatsu, T., Matsubara, M. et al. Crystal structure of a MARCKS peptide containing the calmodulin-binding domain in complex with Ca2+-calmodulin. Nat Struct Mol Biol 10, 226–231 (2003). https://doi.org/10.1038/nsb900

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