# Cryo-EM structure of human AQP11 reveals a trimeric architecture with a large pore

## TL;DR

The human AQP11 protein has a unique trimeric structure with a wide pore, allowing water and small solutes to pass through, offering new insights for drug development.

## Contribution

The first cryo-EM structure of human AQP11 reveals a trimeric architecture and a distinct pore with a novel NPC motif instead of the typical NPA motif.

## Key findings

- Human AQP11 forms a trimeric structure with seven transmembrane helices, including an N-terminal helix.
- The AQP11 pore is broader and more hydrophobic than canonical AQPs, with a unique NPC motif.
- The structure provides a framework for understanding AQP11's transport properties and designing specific inhibitors.

## Abstract

Aquaporin-11 (AQP-11) is an endoplasmic reticulum-localized water channel essential for renal development. Its structure and the molecular basis of its transport properties remained unknown. We analyzed the human AQP11 structure under cryo–electron microscopy at 2.3 Å resolution, revealing a trimeric architecture compared with other known tetrameric AQPs and a topology comprising seven transmembrane helices (Hs), including an additional N-terminal helix (H0). The channel pore is broader and more hydrophobic than that of canonical AQPs, and features a unique structure surrounding an Asn-Pro-Cys (NPC) sequence instead of the typical Asn-Pro-Ala (NPA) motif. These features provide a structural framework through which water and other small solutes can permeate AQP11. Our findings provide a blueprint for designing specific inhibitors to investigate the physiologic functions of AQP11.

The trimeric structure of AQP11 forms a wide pore for water and solutes and offers a previously unknown drug target.