RT Journal Article
SR Electronic
T1 Binding and sequestration of poison frog alkaloids by a plasma globulin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.22.517437
DO 10.1101/2022.11.22.517437
A1 Aurora Alvarez-Buylla
A1 María Dolores Moya Garzón
A1 Alexandra E. Rangel
A1 Elicio E. Tapia
A1 H. Tom Soh
A1 Luis A. Coloma
A1 Jonathan Z. Long
A1 Lauren A. O’Connell
YR 2022
UL http://biorxiv.org/content/early/2022/11/23/2022.11.22.517437.abstract
AB Alkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ∼50 kDa plasma protein is the principal alkaloid binding molecule in blood from poison frogs. Proteomic and biochemical studies establish this plasma protein to be liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid binding activity, ABG sequesters and regulates the bioavailability of “free” plasma alkaloids in vitro. Unexpectedly, ABG is not related to saxiphilin or albumin, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin binding proteins. Alkaloid-binding globulin (ABG) represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points towards serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.Competing Interest StatementThe authors have filed a provisional patent based on the OsABG protein.