Structure of the γ-tubulin ring complex-capped microtubule

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Microtubules, essential for intracellular transport, typically exhibit a 13-protofilament structure.
• The precise mechanism by which cellular microtubules achieve this canonical architecture during assembly remains unclear.
• The gamma-tubulin ring complex (γ-TuRC) is a known regulator of microtubule nucleation.

Purpose of the Study:

• To elucidate the mechanism by which the γ-TuRC nucleates 13-protofilament microtubules.
• To understand how the γ-TuRC establishes the specific lattice architecture of cellular microtubules.
• To investigate the structural dynamics of the γ-TuRC at microtubule minus ends.

Main Methods:

• Cryogenic electron microscopy (Cryo-EM) was used to reconstruct γ-TuRC-capped microtubule minus ends.
• Analysis of the structural dynamics and subunit interactions within the γ-TuRC.
• Investigating the role of γ-TuRC conformation in microtubule nucleation.

Main Results:

• The human ~2.3 MDa γ-TuRC selectively nucleates microtubules with a 13-protofilament structure.
• Cryo-EM revealed extensive intra- and inter-domain motions of γ-TuRC subunits.
• These motions facilitate interactions with luminal bridge components and α/β-tubulin, establishing lateral and longitudinal contacts.

Conclusions:

• The γ-TuRC acts as a crucial determinant of the 13-protofilament architecture in cellular microtubules.
• The γ-TuRC transitions from a splayed conformation to a compacted cap at the microtubule minus end.
• This conformational change dictates the precise lattice arrangement essential for microtubule function.