1497-Structural Principles of CNNM4 Magnesium Transport

The paper describe the discovery of a unique tetrameric structure in the human CNNM4 protein, a vital regulator of magnesium levels in the body. Unlike its bacterial relatives that form simple pairs, human CNNM4 assembles as a dimer of dimers, a complex architecture stabilized by the binding of MgATP. Researchers utilized cryoelectron microscopy to capture the transporter in distinct "outward-facing" and "occluded" states, revealing how the protein transitions to move ions across the cell membrane. A key finding is the identification of an intracellular acidic patch that acts as a sensor, allowing the protein to detect and respond to internal magnesium concentrations. Additionally, the study explains how a specific glutamate residue facilitates the exchange of sodium and magnesium, providing a mechanical framework for understanding human magnesium homeostasis. These insights are medically significant, as they link specific structural defects in CNNM4 to genetic conditions like Jalili syndrome and other physiological disorders.References:Bai Z, Zhou X E, Lü W, et al. Dynamic dimer-of-dimers architecture defines Mg2+ transport in human CNNM4[J]. Cell, 2026.前往小宇宙评论区与主播互动