Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport. / Grønberg, Christina; Sitsel, Oleg; Lindahl, Erik; Gourdon, Pontus; Andersson, Magnus.

In: Biophysical Journal, Vol. 111, No. 11, 06.12.2016, p. 2417-2429.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Grønberg, C, Sitsel, O, Lindahl, E, Gourdon, P & Andersson, M 2016, 'Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport', Biophysical Journal, vol. 111, no. 11, pp. 2417-2429. https://doi.org/10.1016/j.bpj.2016.10.020

APA

Grønberg, C., Sitsel, O., Lindahl, E., Gourdon, P., & Andersson, M. (2016). Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport. Biophysical Journal, 111(11), 2417-2429. https://doi.org/10.1016/j.bpj.2016.10.020

Vancouver

Grønberg C, Sitsel O, Lindahl E, Gourdon P, Andersson M. Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport. Biophysical Journal. 2016 Dec 6;111(11):2417-2429. https://doi.org/10.1016/j.bpj.2016.10.020

Author

Grønberg, Christina ; Sitsel, Oleg ; Lindahl, Erik ; Gourdon, Pontus ; Andersson, Magnus. / Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport. In: Biophysical Journal. 2016 ; Vol. 111, No. 11. pp. 2417-2429.

Bibtex

@article{0cf6bebf3b3e4cdb940799ffc7611a04,

title = "Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport",

abstract = "Cu(+)-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu(+)-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu(+) entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu(+) delivery. Mutational analyses and simulations in the presence and absence of Cu(+) predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu(+)-transporting P-type ATPases.",

author = "Christina Gr{\o}nberg and Oleg Sitsel and Erik Lindahl and Pontus Gourdon and Magnus Andersson",

year = "2016",

month = dec,

day = "6",

doi = "10.1016/j.bpj.2016.10.020",

language = "English",

volume = "111",

pages = "2417--2429",

journal = "Biophysical Journal",

issn = "0006-3495",

publisher = "Cell Press",

number = "11",

}

RIS

TY - JOUR

T1 - Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport

AU - Grønberg, Christina

AU - Sitsel, Oleg

AU - Lindahl, Erik

AU - Gourdon, Pontus

AU - Andersson, Magnus

PY - 2016/12/6

Y1 - 2016/12/6

N2 - Cu(+)-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu(+)-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu(+) entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu(+) delivery. Mutational analyses and simulations in the presence and absence of Cu(+) predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu(+)-transporting P-type ATPases.

AB - Cu(+)-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu(+)-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu(+) entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu(+) delivery. Mutational analyses and simulations in the presence and absence of Cu(+) predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu(+)-transporting P-type ATPases.

U2 - 10.1016/j.bpj.2016.10.020

DO - 10.1016/j.bpj.2016.10.020

M3 - Journal article

C2 - 27926843

VL - 111

SP - 2417

EP - 2429

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 11

ER -

ID: 173100356