Homology modeling and in vivo functional characterization of the zinc permeation pathway in a heavy metal P-type ATPase

Three-dimensional modeling of the HMA4 protein in Arabidopsis reveals the zinc permeation pathway across the plasma membrane, and mutations in the pathway alter zinc and cadmium transport differently in plants. Abstract The P1B ATPase heavy metal ATPase 4 (HMA4) is responsible for zinc and cadmium t...

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Bibliographic Details
Published in:Journal of experimental botany 2019-01, Vol.70 (1), p.329-341
Main Authors: Lekeux, Gilles, Crowet, Jean-Marc, Nouet, Cécile, Joris, Marine, Jadoul, Alice, Bosman, Bernard, Carnol, Monique, Motte, Patrick, Lins, Laurence, Galleni, Moreno, Hanikenne, Marc
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Arabidopsis - enzymology
Arabidopsis - genetics
Arabidopsis - metabolism
Arabidopsis Proteins - genetics
Arabidopsis Proteins - metabolism
Biochemistry, biophysics & molecular biology
Biochimie, biophysique & biologie moléculaire
Biological Transport
HMA4
homology modelling
in vivo imaging
Life Sciences
Models, Genetic
molecular dynamics
P-type ATPase
Quantitative Methods
Research Papers
Sciences du vivant
Structural Homology, Protein
Vegetal Biology
Zinc - metabolism
Zinc transport
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Summary:Three-dimensional modeling of the HMA4 protein in Arabidopsis reveals the zinc permeation pathway across the plasma membrane, and mutations in the pathway alter zinc and cadmium transport differently in plants. Abstract The P1B ATPase heavy metal ATPase 4 (HMA4) is responsible for zinc and cadmium translocation from roots to shoots in Arabidopsis thaliana. It couples ATP hydrolysis to cytosolic domain movements, enabling metal transport across the membrane. The detailed mechanism of metal permeation by HMA4 through the membrane remains elusive. Here, homology modeling of the HMA4 transmembrane region was conducted based on the crystal structure of a ZntA bacterial homolog. The analysis highlighted amino acids forming a metal permeation pathway, whose importance was subsequently investigated functionally through mutagenesis and complementation experiments in plants. Although the zinc pathway displayed overall conservation among the two proteins, significant differences were observed, especially in the entrance area with altered electronegativity and the presence of a ionic interaction/hydrogen bond network. The analysis also newly identified amino acids whose mutation results in total or partial loss of the protein function. In addition, comparison of zinc and cadmium accumulation in shoots of A. thaliana complemented lines revealed a number of HMA4 mutants exhibiting different abilities in zinc and cadmium translocation. These observations could be instrumental to design low cadmium-accumulating crops, hence decreasing human cadmium exposure.
ISSN:0022-0957
1460-2431
1460-2431
DOI:10.1093/jxb/ery353