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Crystal structure of a scavenger receptor cysteine-rich domain sheds light on an ancient superfamily

Nature Structural Biology volume 6, pages 228–232 (1999)Cite this article

Abstract

Scavenger receptor cysteine-rich (SRCR) domains are found widely in cell surface molecules and in some secreted proteins, where they are thought to mediate ligand binding. We have determined the crystal structure at 2.0 Å resolution of the SRCR domain of Mac-2 binding protein (M2BP), a tumor-associated antigen and matrix protein. The structure reveals a curved six-stranded β-sheet cradling an α-helix. Structure-based sequence alignment demonstrates that the M2BP SRCR domain is a valid template for the entire SRCR protein superfamily. This allows an interpretation of previous mutagenesis data on ligand binding to the lymphocyte receptor CD6.

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Figure 1: Two orthogonal views32 of the M2BP SRCR domain structure.
Figure 2: Analysis of the SRCR domain superfamily2,3,4.
Figure 3: Stereo Cα drawing of a superposition of M2BP SRCR (in red) and scorpion toxin II (ref.24; in blue).
Figure 4: Stereo view of the experimental electron density map after solvent flattening at 3.0 Å resolution.

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Acknowledgements

We thank C. Slingsby for critically reading the manuscript. E.H. is supported by a long-term fellowship from the Human Frontier Science Program. R.T. acknowledges financial support from an EC grant.

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Authors and Affiliations

  1. Department of Crystallography, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, UK

    Erhard Hohenester

  2. Abteilung Proteinchemie, Max-Planck-Institut für Biochemie, Martinsried, D-82152, Germany

    Takako Sasaki & Rupert Timpl

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  1. Erhard Hohenester
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Correspondence to Erhard Hohenester.

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Hohenester, E., Sasaki, T. & Timpl, R. Crystal structure of a scavenger receptor cysteine-rich domain sheds light on an ancient superfamily. Nat Struct Mol Biol 6, 228–232 (1999). https://doi.org/10.1038/6669

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