CryoEM structure of the super-constricted two-start dynamin 1 filament

Jiwei Liu,Peijun Zhang,Jeffrey K Noel,Daniel K Clare,Frances Joan D Alvarez

doi:10.1038/s41467-021-25741-x

Abstract

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis. Dynamin molecules are recruited to the neck of budding vesicles to assemble into a helical collar and to constrict the underlying membrane. Two helical forms were observed: the one-start helix in the constricted state and the two-start helix in the super-constricted state. Here we report the cryoEM structure of a super-constricted two-start dynamin 1 filament at 3.74 Å resolution. The two strands are joined by the conserved GTPase dimeric interface. In comparison with the one-start structure, a rotation around Hinge 1 is observed, essential for communicating the chemical power of the GTPase domain and the mechanical force of the Stalk and PH domain onto the underlying membrane. The Stalk interfaces are well conserved and serve as fulcrums for adapting to changing curvatures. Relative to one-start, small rotations per interface accumulate to bring a drastic change in the helical pitch. Elasticity theory rationalizes the diversity of dynamin helical symmetries and suggests corresponding functional significance.

Highlights

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis
Domain), which binds and hydrolyzes GTP; (ii) the bundlesignaling element (BSE), which transmits the two-way signaling between the catalytic domain and Stalk domain; (iii) the Stalk domain, which provides major interfaces for oligomerization; (iv) the pleckstrin homology (PH) domain, which targets dynamin to the membrane; and (v) the proline-rich (PRD) domain, which binds SH3-containing partner proteins at the fission site[7,8]
Various cryoEM reconstructions confirmed that a GG dimer interface forms between two dynamin monomers in helical configurations, and the three conserved Stalk interfaces are vital for dynamin to polymerize into filaments[12,13]

Summary

Introduction

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis. The crystal structures show that two Stalk domains form a cross dimer through the conserved interface 2. Various cryoEM reconstructions confirmed that a GG dimer interface forms between two dynamin monomers in helical configurations, and the three conserved Stalk interfaces are vital for dynamin to polymerize into filaments[12,13]. During the cycles of GTP hydrolysis (GTPase cycles), the GG dimer forms and dissociates repeatedly, and the energies from the hydrolysis by the dynamin helical coat drives the scission of the underlying membrane[13,14]

Methods

Results

Conclusion