# Dimerization of the BAR domain–containing protein FAM92A modulates lipid binding and interaction with CBY1

## TL;DR

This study reveals how the FAM92A protein dimerizes and interacts with CBY1, shedding light on its role in shaping cell membranes and ciliary assembly.

## Contribution

The paper presents the crystal structure of FAM92A's BAR domain and identifies key residues involved in lipid binding and dimerization.

## Key findings

- The mouse FAM92A BAR domain forms an antiparallel homodimer with a crescent shape.
- Positively charged clusters on the concave surface are essential for lipid binding and dimerization.
- FAM92A BAR directly binds to CBY1, with dimerization enhancing their interaction affinity.

## Abstract

BAR (Bin/Amphiphysin/Rvs) domain proteins drive membrane remodeling critical for cellular processes like ciliogenesis and organelle morphology. FAM92A (family with sequence similarity 92A), a classical BAR protein, regulates ciliary assembly, mitochondrial ultrastructure, and neuronal membrane dynamics, yet its molecular mechanisms remain elusive. Here, we determined the 2.2 Å crystal structure of the mouse FAM92A BAR domain, revealing an antiparallel, crescent-shaped homodimer. Structure-guided mutagenesis revealed that positively charged clusters on the concave surface are critical for lipid binding and identified residues essential for dimerization. We further demonstrated that FAM92A BAR directly binds the N-terminal region of Chibby1 (CBY1), a ciliary protein, with their respective dimerizations synergistically enhancing affinity. These findings elucidate the structural basis of FAM92A’s membrane remodeling and CBY1 interaction, providing a molecular framework for its function in ciliogenesis and suggesting broader implications for FAM92 family proteins.