# Cryogenic electron tomography reveals helical organization of lipoprotein lipase in storage vesicles

## TL;DR

Scientists used cryo-ET and cryo-EM to discover that lipoprotein lipase forms inactive filaments inside storage vesicles before being secreted.

## Contribution

The study reveals the first detailed structure of inactive lipoprotein lipase in storage vesicles using cryo-ET and cryo-EM.

## Key findings

- Lipoprotein lipase forms 11-nanometer filaments in storage vesicles.
- The filaments have occluded active sites, making LPL inactive in storage.
- Cryo-ET and cryo-EM confirmed the inactive filament as the physiological storage form of LPL.

## Abstract

Lipoprotein lipase (LPL) is a triglyceride lipase that is contained in intracellular vesicles in an inactive storage form before secretion, but the precise structural details have not yet been resolved. Using cryo–electron tomography (cryo-ET), we observe that LPL exists inside of storage vesicles as a filament with an 11-nanometer diameter and is packed in these vesicles in two distinct patterns. Next, we solved a 4.2-Å resolution cryo–electron microscopy (cryo-EM) structure of this 11-nanometer LPL filament using purified protein. The filament is made of repeating pairs of LPL molecules with occluded active sites, rendering the LPL inactive. The comparison of the in situ subtomogram average and the in vitro cryo-EM structure indicates that the previously uncharacterized physiological storage form of LPL is an inactive filament.

Cryo-ET and cryo-EM show that lipoprotein lipase forms an inactive, filamentous storage structure in vesicles.