Myosin MyTH4-FERM structures highlight important principles of convergent evolution

Area of Science:

• Molecular Biology
• Cell Biology
• Evolutionary Biology

Background:

• Myosins with MyTH4-FERM (MF) domains are present in diverse organisms, from humans to Dictyostelium.
• These MF myosins are crucial for actin-filled membrane protrusions (e.g., filopodia) and microtubule binding.
• Their conserved roles suggest a highly preserved core function throughout evolution.

Purpose of the Study:

• To investigate the structural conservation and divergence of MF domains in myosins.
• To understand how structural modifications in MF domains influence their function and binding partners.
• To explore the evolutionary mechanisms, such as convergent evolution, shaping MF myosin functions.

Main Methods:

• Determining the structures of MF domains from Dictyostelium Myo7 (DdMyo7).
• Comparing these structures with known mammalian MF domain structures.
• Analyzing diverse MF myosin sequences to identify conserved and divergent features.

Main Results:

• MF domains exhibit conserved structural features across species, despite millions of years of evolution.
• Class-specific insertions alter MF domain surfaces and subdomain orientations, creating new binding sites.
• MyTH4 domains of Myo10 and DdMyo7 bind microtubules on opposite surfaces, indicating functional adaptation.

Conclusions:

• Myosin tail domain features can be maintained without strict motif conservation, allowing functional adaptation.
• Tuning of existing MF domain features generates new structures while preserving essential properties.
• MF domains act as multifunctional platforms, with conserved functions like autoinhibition and microtubule binding arising via convergent evolution.