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Profilin binds proline-rich ligands in two distinct amide backbone orientations

Nature Structural Biology volume 6, pages 666–671 (1999)Cite this article

Abstract

The actin regulatory protein profilin is targeted to specific cellular regions through interactions with highly proline-rich motifs embedded within its binding partners. New X-ray crystallographic results demonstrate that profilin, like SH3 domains, can bind proline-rich ligands in two distinct amide backbone orientations. By further analogy with SH3 domains, these data suggest that non-proline residues in profilin ligands may dictate the polarity and register of binding, and the detailed organization of the assemblies involving profilin. This degeneracy may be a general feature of modules that bind proline-rich ligands, including WW and EVH1 domains, and has implications for the assembly and activity of macromolecular complexes involved in signaling and the regulation of the actin cytoskeleton.

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Figure 1: Proline-rich sequences in proteins implicated in profilin binding through genetic and/or biochemical studies.
Figure 2: Simulated annealing omit maps of the HPP–L-Pro10-iodo-tyrosine complex structure and comparison with the HPP–L-Pro10 structure.
Figure 3: Electron density of the HMC-L-Pro15 peptide and the asymmetric unit of the HPP–HMC-L-Pro15 complex.
Figure 4: Detailed comparison of the two peptide binding polarities.

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Acknowledgements

This work was supported by awards from the National Institutes of Health to S.C.A. N.M.M. was supported by a training grant from the National Institutes of Health.

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  1. Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA

    Nicole M. Mahoney, Denise A. Rozwarski, Elena Fedorov, Alexander A. Fedorov & Steven C. Almo

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Mahoney, N., Rozwarski, D., Fedorov, E. et al. Profilin binds proline-rich ligands in two distinct amide backbone orientations. Nat Struct Mol Biol 6, 666–671 (1999). https://doi.org/10.1038/10722

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