Year: 2018
Type: article
Abstract: Ferroportin (Fpn)—the only known cellular iron exporter—transports dietary and recycled iron into the blood plasma, and transfers iron across the placenta. Despite its central role in iron metabolism, our molecular understanding of Fpn-mediated iron efflux remains incomplete. Here, we report that Ca2+ is required for human Fpn transport activity. Whereas iron efflux is stimulated by extracellular Ca2+ in the physiological range, Ca2+ is not transported. We determine the crystal structure of a Ca2+-bound BbFpn, a prokaryotic orthologue, and find that Ca2+ is a cofactor that facilitates a conformational change critical to the transport cycle. We also identify a substrate pocket accommodating a divalent transition metal complexed with a chelator. These findings support a model of iron export by Fpn and suggest a link between plasma calcium and iron homeostasis.
Source: Nature Communications
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1188863548, G166906552, G295821465, Divalent metal-ion transporter DMT1 and its role in intestinal metal-ion uptake, Mechanism of anoxic iron acquisition in pathogenic bacteria, Ferroportin Structure and function, The Hepcidin-Ferroportin Axis in Anemia of Inflammation: Mechanisms and Targets, G5659890370, G7172642422, G7554021396, G9000087880, G9000295917
OpenAlex ID: W2885078443