Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin

Elife. 2016 Jan 19;5:e12856. doi: 10.7554/eLife.12856.

Abstract

Class III myosins (Myo3) and actin-bundling protein Espin play critical roles in regulating the development and maintenance of stereocilia in vertebrate hair cells, and their defects cause hereditary hearing impairments. Myo3 interacts with Espin1 through its tail homology I motif (THDI), however it is not clear how Myo3 specifically acts through Espin1 to regulate the actin bundle assembly and stabilization. Here we discover that Myo3 THDI contains a pair of repeat sequences capable of independently and strongly binding to the ankyrin repeats of Espin1, revealing an unexpected Myo3-mediated cross-linking mechanism of Espin1. The structures of Myo3 in complex with Espin1 not only elucidate the mechanism of the binding, but also reveal a Myo3-induced release of Espin1 auto-inhibition mechanism. We also provide evidence that Myo3-mediated cross-linking can further promote actin fiber bundling activity of Espin1.

Keywords: Espin; actin bundles; biophysics; cell biology; myosin III; structural biology; unconventional myosin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Crystallography, X-Ray
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism*
  • Models, Molecular
  • Myosin Heavy Chains / chemistry
  • Myosin Heavy Chains / metabolism*
  • Myosin Type III / chemistry
  • Myosin Type III / metabolism*
  • Protein Conformation
  • Protein Multimerization*

Substances

  • Actins
  • ESPN protein, human
  • MYO3B protein, human
  • Microfilament Proteins
  • MYO3A protein, human
  • Myosin Type III
  • Myosin Heavy Chains

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.