Zinc is carried through the body by a protein known as serum albumin. Scientists proved the location of the primary site where serum albumin binds with zinc, but the team also found several more secondary binding sites, revealing a more complex interaction than anticipated.
While computer models previously had been used to predict how serum albumin picks up zinc, the team used X-ray macromolecular crystallography to obtain data-based images of protein crystals showing how zinc actually bound to serum albumin. The technique allowed them to pinpoint the location of each particular zinc atom, though it was a challenging task. The schematics produced allow scientists to see, for the first time, exactly how serum albumin and zinc come together. Serum albumin also transports many other things, such as hormones and fatty acids.
Too much zinc is toxic to the body, so it must make zinc available where it is needed, but prevent harmful, excessive buildup. The study’s findings could help shed light on why certain drugs affect some patients differently than others.
Handing, K. B., et al. “Circulatory Zinc Transport is Controlled by Distinct Interdomain Sites on Mammalian Albumins.” Chem. Sci. 7, 6635 (2016). [DOI:10.1039/c6sc02267g].
Instruments and Facilities Used: X-ray macromolecular crystallography; Life Sciences Collaborative Access Team (LS-CAT) 21-ID-F and 21-ID-G X-ray beamlines and Structural Biology Center (SBC)-CAT 19-BM-D X-ray beamline, all at the Advanced Photon Source at Argonne National Laboratory.
Funding Acknowledgements: Structural data used resources of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory (ANL) under Contract No. DE-AC02-06CH11357. Use of LS-CAT Sector 21 supported by Michigan Economic Development Corporation and Michigan Technology Tri-Corridor (Grant 085P1000817). Work supported by NIH grants 1R01GM117325-01, 5U54GM094662-05, and R01GM053163; BBSRC grant BB/J006467/1; and British Heart Foundation grant PG/15/9/31270.