| Structural highlights
Function
FIEF_SHEON Divalent metal cation transporter which exports Zn(2+), Cd(2+) and possibly Fe(2+) (PubMed:23341604, PubMed:29507252). Zn(2+)/H(+) antiporter capable of using the proton motive force to remove Zn(2+) from the cytoplasm (PubMed:34254979). May be involved in zinc and iron detoxification by efflux (By similarity).[UniProtKB:P69380][1] [2] [3]
Publication Abstract from PubMed
YiiP is a secondary transporter that couples Zn2+ transport to the proton motive force. Structural studies of YiiP from prokaryotes and Znt8 from humans have revealed three different Zn2+ sites and a conserved homodimeric architecture. These structures define the inward-facing and outward-facing states that characterize the archetypal alternating access mechanism of transport. To study the effects of Zn2+ binding on the conformational transition, we use cryo-EM together with molecular dynamics simulation to compare structures of YiiP from Shewanella oneidensis in the presence and absence of Zn2+. To enable single-particle cryo-EM, we used a phage-display library to develop a Fab antibody fragment with high affinity for YiiP, thus producing a YiiP/Fab complex. To perform MD simulations, we developed a nonbonded dummy model for Zn2+ and validated its performance with known Zn2+-binding proteins. Using these tools, we find that, in the presence of Zn2+, YiiP adopts an inward-facing conformation consistent with that previously seen in tubular crystals. After removal of Zn2+ with high-affinity chelators, YiiP exhibits enhanced flexibility and adopts a novel conformation that appears to be intermediate between inward-facing and outward-facing states. This conformation involves closure of a hydrophobic gate that has been postulated to control access to the primary transport site. Comparison of several independent cryo-EM maps suggests that the transition from the inward-facing state is controlled by occupancy of a secondary Zn2+ site at the cytoplasmic membrane interface. This work enhances our understanding of individual Zn2+ binding sites and their role in the conformational dynamics that govern the transport cycle.
Zinc binding alters the conformational dynamics and drives the transport cycle of the cation diffusion facilitator YiiP.,Lopez-Redondo M, Fan S, Koide A, Koide S, Beckstein O, Stokes DL J Gen Physiol. 2021 Aug 2;153(8):e202112873. doi: 10.1085/jgp.202112873. Epub , 2021 Jul 13. PMID:34254979[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Coudray N, Valvo S, Hu M, Lasala R, Kim C, Vink M, Zhou M, Provasi D, Filizola M, Tao J, Fang J, Penczek PA, Ubarretxena-Belandia I, Stokes DL. Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy. Proc Natl Acad Sci U S A. 2013 Jan 22. PMID:23341604 doi:http://dx.doi.org/10.1073/pnas.1215455110
- ↑ Lopez-Redondo ML, Coudray N, Zhang Z, Alexopoulos J, Stokes DL. Structural basis for the alternating access mechanism of the cation diffusion facilitator YiiP. Proc Natl Acad Sci U S A. 2018 Mar 5. pii: 1715051115. doi:, 10.1073/pnas.1715051115. PMID:29507252 doi:http://dx.doi.org/10.1073/pnas.1715051115
- ↑ Lopez-Redondo M, Fan S, Koide A, Koide S, Beckstein O, Stokes DL. Zinc binding alters the conformational dynamics and drives the transport cycle of the cation diffusion facilitator YiiP. J Gen Physiol. 2021 Aug 2;153(8):e202112873. PMID:34254979 doi:10.1085/jgp.202112873
- ↑ Lopez-Redondo M, Fan S, Koide A, Koide S, Beckstein O, Stokes DL. Zinc binding alters the conformational dynamics and drives the transport cycle of the cation diffusion facilitator YiiP. J Gen Physiol. 2021 Aug 2;153(8):e202112873. PMID:34254979 doi:10.1085/jgp.202112873
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