8AP5

Cadmium-loaded form of Caenorhabditis elegans MTL-2

Summary for 8AP5

• Entry DOI: 10.2210/pdb8ap5/pdb
• NMR Information: BMRB: 51546
• Descriptor: Metallothionein-2, CADMIUM ION (2 entities in total)
• Functional Keywords: structure from cyana 2.1 metallothionein zinc cadmium c. elegans, metal binding protein
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 1
• Total formula weight: 6939.88

Authors

Leszczyszyn, O.I.,Sturzenbaum, S.R.,Blindauer, C.A. (deposition date: 2022-08-09, release date: 2024-01-17)

Primary citation

Essig, Y.J.,Leszczyszyn, O.I.,Almutairi, N.,Harrison-Smith, A.,Blease, A.,Zeitoun-Ghandour, S.,Webb, S.M.,Blindauer, C.A.,Sturzenbaum, S.R.
Juggling cadmium detoxification and zinc homeostasis: A division of labour between the two C. elegans metallothioneins.
Chemosphere, 350:141021-141021, 2023

PubMed Abstract: The chemical properties of toxic cadmium and essential zinc are very similar, and organisms require intricate mechanisms that drive selective handling of metals. Previously regarded as unspecific "metal sponges", metallothioneins (MTLs) are emerging as metal selectivity filters. By utilizing C. elegans mtl-1 and mtl-2 knockout strains, metal accumulation in single worms, single copy fluorescent-tagged transgenes, isoform specific qPCR and lifespan studies it was possible to demonstrate that the handling of cadmium and zinc by the two C. elegans metallothioneins differs fundamentally: the MTL-2 protein can handle both zinc and cadmium, but when it becomes unavailable, either via a knockout or by elevated cadmium exposure, MTL-1 takes over zinc handling, leaving MTL-2 to sequester cadmium. This division of labour is reflected in the folding behaviour of the proteins: MTL-1 folded well in presence of zinc but not cadmium, the reverse was the case for MTL-2. These differences are in part mediated by a zinc-specific mononuclear HisCys site in the C-terminal insertion of MTL-1; its removal affected the entire C-terminal domain and may shift its metal selectivity towards zinc. Overall, we uncover how metallothionein isoform-specific responses and protein properties allow C. elegans to differentiate between toxic cadmium and essential zinc.

PubMed: 38151062
DOI: 10.1016/j.chemosphere.2023.141021

Experimental method

SOLUTION NMR