TY - JOUR
T1 - Cation diffusion facilitators transport initiation and regulation is mediated by cation induced conformational changes of the cytoplasmic domain
AU - Zeytuni, Natalie
AU - Uebe, René
AU - Maes, Michal
AU - Davidov, Geula
AU - Baram, Michal
AU - Raschdorf, Oliver
AU - Nadav-Tsubery, Merav
AU - Kolusheva, Sofiya
AU - Bitton, Ronit
AU - Goobes, Gil
AU - Friedler, Assaf
AU - Miller, Yifat
AU - Schüler, Dirk
AU - Zarivach, Raz
PY - 2014/3/21
Y1 - 2014/3/21
N2 - Cation diffusion facilitators (CDF) are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all domains of life. CDF's were shown to be involved in several human diseases, such as Type-II diabetes and neurodegenerative diseases. In this work, we employed a multi-disciplinary approach to study the activation mechanism of the CDF protein family. For this we used MamM, one of the main ion transporters of magnetosomes - bacterial organelles that enable magnetotactic bacteria to orientate along geomagnetic fields. Our results reveal that the cytosolic domain of MamM forms a stable dimer that undergoes distinct conformational changes upon divalent cation binding. MamM conformational change is associated with three metal binding sites that were identified and characterized. Altogether, our results provide a novel auto-regulation mode of action model in which the cytosolic domain's conformational changes upon ligand binding allows the priming of the CDF into its transport mode.
AB - Cation diffusion facilitators (CDF) are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all domains of life. CDF's were shown to be involved in several human diseases, such as Type-II diabetes and neurodegenerative diseases. In this work, we employed a multi-disciplinary approach to study the activation mechanism of the CDF protein family. For this we used MamM, one of the main ion transporters of magnetosomes - bacterial organelles that enable magnetotactic bacteria to orientate along geomagnetic fields. Our results reveal that the cytosolic domain of MamM forms a stable dimer that undergoes distinct conformational changes upon divalent cation binding. MamM conformational change is associated with three metal binding sites that were identified and characterized. Altogether, our results provide a novel auto-regulation mode of action model in which the cytosolic domain's conformational changes upon ligand binding allows the priming of the CDF into its transport mode.
UR - http://www.scopus.com/inward/record.url?scp=84899090594&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0092141
DO - 10.1371/journal.pone.0092141
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C2 - 24658343
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e92141
ER -