Membrane Constriction by Dynamin through GTP-Driven Conformational Changes from Coarse-Grained Molecular Dynamics...

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Dynamin is a GTPase essential for membrane remodeling and fission during endocytosis.
• Understanding dynamin's assembly and GTP hydrolysis-induced conformational changes is key to membrane constriction mechanisms.
• The complexity of dynamin assemblies hinders comprehensive molecular mechanism studies.

Purpose of the Study:

• To elucidate the chemo-mechanical coupling mechanism of dynamin-mediated membrane constriction.
• To investigate dynamin's conformational changes on lipid membranes using molecular dynamics simulations.

Main Methods:

• Coarse-grained molecular dynamics (CG-MD) simulations using the Martini force field.
• Simulation of dynamin rings on a tubular membrane with controlled length via pressure coupling.
• Analysis of nucleotide-state-dependent conformational changes.

Main Results:

• Dynamin ring conformational changes to the GDP state were observed.
• These changes lead to loosening and expansion of dynamin rings.
• Indirect membrane constriction in protein-uncoated regions was identified as a consequence.

Conclusions:

• The study provides insights into the chemo-mechanical coupling of dynamin.
• Simulations suggest indirect membrane constriction driven by dynamin ring dynamics.
• This work establishes a foundation for further simulations of dynamin-mediated membrane processes.