Yashab's Notes

Formins

2 min read

Formins are a diverse set of homodimers containing an IDR — the FH1 domain that facilitates polymerization of the cytoskeletal protein actin by increasing the local concentration of actin monomers at the actin assembly site.

A good explanation of Formin’s role in actin polymerization:

https://youtu.be/pKbC-cI3sDw?si=hQY_17PJXRRbaQ9Q
Title: Actin Nucleation By Formin Protein | Actin Binding Proteins |
Author: BMH learning
Thumbnail: https://i.ytimg.com/vi/pKbC-cI3sDw/mqdefault.jpg
AuthorUrl: https://www.youtube.com/@BMHlearning

Structure

Domain structure of Formin proteins across phyla

By Peteruetz - Own work, CC BY-SA 4.0, Link center

The “Donut” (FH2 Domain)

The FH2 domain forms a stable, donut-shaped homodimer that acts as the “anchor”. It performs two critical roles:

  • Nucleation: It stabilizes the initial “seed” of actin monomers to start a new filament.
  • Processive Tracking: It stays attached to the fast-growing “barbed end” of the filament as it grows, moving along with it without detaching.

Flashcards

The FH2 domain of formins act as an anchor to the polymerizing actin filament.

Formins need to come together as a homodimer at FH2 domains to be able to function as polymerization promoting factor of F-actin.

The “Grabby Arms” (FH1 Domain)

The FH1 domains are long, flexible, “intrinsically disordered” regions that extend from the FH2 anchor like long arms. They contain multiple proline-rich motifs (PRMs), which serve as binding sites for the protein profilin when it is bound to an actin monomer.

Flashcards

Which domain of Formins is proline rich?::FH1 domain

The FH1 domain is proline-rich which serves as the binding site for ATP-actin.

Function

Capture and Deliver

  • Capture Step: The flexible FH1 arms reach into the surrounding solution to “grab” profilin-actin complexes using their PRM binding sites.
  • Delivery Step: Once captured, the FH1 arm physically moves to bring the actin monomer to the FH2 domain. This increases the local concentration of actin at the assembly site, allowing the filament to grow much faster than it would through random diffusion alone.

Graph View

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