Interactions between TTYH2 and APOE facilitate endosomal lipid transfer

Abstract
The Tweety homologues (TTYHs) constitute a family of eukaryotic membrane proteins that, on the basis of structural features, were recently proposed to contribute to lipid transfer between soluble carriers and cellular membranes1. However, in the absence of supporting data, this function was hypothetical. Here through pull-down of endogenous proteins, we identify APOE as the interaction partner of human TTYH2. Subcellular fractionation and immunocytochemistry assays showed that both proteins colocalize in endosomal compartments. Characterization of the specific interaction between APOE and TTYH2 through binding assays and structural studies enabled us to identify an epitope in an extended domain of TTYH2 that faces the endosomal lumen. Structures of complexes with APOE-containing lipoprotein particles revealed a binding mode that places lipids in a suitable position to facilitate their diffusion into the membrane. Moreover, in vitro studies revealed that lipid tra..., , # Data from: Interactions between TTYH2 and APOE facilitate endosomal lipid transfer

Dataset DOI: [10.5061/dryad.kprr4xhhz](10.5061/dryad.kprr4xhhz)

## Description of the data and file structure

Confocal microscopy images for: Interactions between TTYH2 and ApoE facilitate endosomal lipid transfer.

Raw data for confocal microscopy images from Figure 2b, 2c; Extended Data Figure 3a-c; Extended Data Figure 9m. The .czi files contain stacks of images aquired from distinct areas using the ZEN software on a Zeiss LSM 980 Airyscan inverted confocal laser scanning microscope. The metadata for each file can be accessed by opening the files using FIJI -> Image -> Show info.

The .czi files can be opened using FIJI.

### Files and variables

#### File: Figure_2b.czi

**Description:** Raw data for Figure 2b showing HEK293T cells stained with anti-TTYH2 antibody and DAPI. The primary purpose of the Figure 2b was to illustrate the intracellular localization of TTYH2. However, ApoE-mCherry lipopr...,