The yeast dynein Dyn2-Pac11 complex is a dynein dimerization/processivity factor: structural and single-molecule...

Area of Science:

• Molecular motor function
• Cellular transport mechanisms
• Protein complex structure and dynamics

Background:

• Cytoplasmic dynein is the primary microtubule motor for minus-end directed transport.
• The regulatory roles of dynein's N-terminal tail and accessory chains are not fully understood.
• Understanding these accessory chains is key to elucidating dynein motor regulation.

Purpose of the Study:

• To investigate the structure and function of Saccharomyces cerevisiae dynein light (Dyn2) and intermediate (Pac11) chains.
• To determine how Dyn2 and Pac11 influence the motor activity of dynein heavy chain (Dyn1).
• To explore the conserved regulatory role of the dynein N-terminal region.

Main Methods:

• Crystal structure determination of the Dyn2-Pac11 complex.
• Generation of yeast strains with deletions in dyn2 and pac11 genes (dyn2Δ, dyn2Δpac11Δ).
• Single-molecule analysis of Dyn1 motor activity in different genetic backgrounds.

Main Results:

• The Dyn2-Pac11 complex facilitates Dyn1 homodimerization and enhances processivity.
• Absence of Dyn2 and Pac11 leads to reduced Dyn1 velocity, decreased processivity, and increased aggregation.
• Depletion of Dyn2 and Pac11 results in Dyn1 motor phenotypes similar to mammalian dynein N-terminal mutations (Loa).

Conclusions:

• The Dyn2-Pac11 complex is essential for optimal Dyn1 motor function, including dimerization and processivity.
• The N-terminal accessory chains play a critical conserved role in regulating cytoplasmic dynein motor activity.
• This study highlights the N-terminal region as a key regulatory element in dynein function across species.