Myosins containing MyTH4-FERM (myosin tail homology 4-band 4.1, ezrin, radixin, moesin, or MF) domains in their tails are found in a wide range of phylogenetically divergent organisms, such as humans and the social amoeba Dictyostelium (Dd). Interestingly, evolutionarily distant MF myosins have similar roles in the extension of actin-filled membrane protrusions such as filopodia and bind to microtubules (MT), suggesting that the core functions of these MF myosins have been highly conserved over evolution. The structures of two DdMyo7 signature MF domains have been determined and comparison with mammalian MF structures reveals that characteristic features of MF domains are conserved. However, across millions of years of evolution conserved class-specific insertions are seen to alter the surfaces and the orientation of subdomains with respect to each other, likely resulting in new sites for binding partners. The MyTH4 domains of Myo10 and DdMyo7 bind to MT with micromolar affinity but, surprisingly, their MT binding sites are on opposite surfaces of the MyTH4 domain. The structural analysis in combination with comparison of diverse MF myosin sequences provides evidence that myosin tail domain features can be maintained without strict conservation of motifs. The results illustrate how tuning of existing features can give rise to new structures while preserving the general properties necessary for myosin tails. Thus, tinkering with the MF domain enables it to serve as a multifunctional platform for cooperative recruitment of various partners, allowing common properties such as autoinhibition of the motor and microtubule binding to arise through convergent evolution.
|Original language||English (US)|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - May 24 2016|
Bibliographical noteFunding Information:
ACKNOWLEDGMENTS. We thank Pierre Legrand and Andrew Thompson and beamline scientists of PROXIMA1 and PROXIMA2 (SOLEIL synchrotron) for excellent support during data collection; Dr. Holly Goodson (University of Notre Dame), Dr. Daniel Picot, Dr. Isabelle Callebaut, and Karl Petersen for comments on the manuscript; and Karl Petersen for assistance with the alignments. This work was supported by NIH Grant R37 GM054141 (to S.P.G.) and the Fondation pour la Recherche M?dicale (FRM) (M.C.). This project was granted access to the high-performance computing resources of Centre Informatique National de l'Enseignement Sup?rieur under Allocation2015076644 made by Grand ?quipement National de Calcul Intensif. A.H. was supported by grants from the Centre National de la Recherche Scientifique, ANR-13-BSV8-0019-01, FRM, Ligue Nationale Contre le Cancer, and Association pour la Recherche sur le Cancer Subvention Fixe. The A.H. team is part of Labex CelTisPhyBio 11-LBX-0038, which is part of the Initiative d'Excellence at PSL Research University (ANR-10-IDEX-0001-02 PSL). M.A.T. was supported by National Science Foundation Grants MCB-0923743 and MCB-1244235.
- Molecular tinkering
- Protein evolution