Human Transporter De-oligomerization Regulates Copper Uptake into Cells

Overview

Journal Res Sq

Date 2024 Dec 23

PMID 39711524

Authors

Tai-Yen Chen

Meng-Hsuan Wen

Huanhuan Chen

Guangjie Yan

Yuteng Zhang

Wenkai Chen

Martin Dokholyan

Jian Wang

Nikolay Dokholyan

Affiliations

Soon will be listed here.

Abstract

Copper is an essential element involved in various biochemical processes, such as mitochondrial energy production and antioxidant defense, but improper regulation can lead to cellular toxicity and disease. Copper Transporter 1 (CTR1) plays a key role in copper uptake and maintaining cellular copper homeostasis. Although CTR1 endocytosis was previously thought to reduce copper uptake when levels are high, it was unclear how rapid regulation is achieved. Using single-molecule localization microscopy and single-molecule neighbor density assays, we discovered that excess copper induces monomerization of the wild-type trimeric CTR1 prior to endocytosis, a response blocked in the endocytosis-deficient CTR1 (M150L) mutant. This monomerization rapidly halts copper uptake and prevents copper overload. These findings reveal changes in protein oligomerization as a new paradigm of metal transport regulation, linking CTR1's structural changes to its endocytosis and copper homeostasis.

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