A Cadmium-transporting P1B-type ATPase in Yeast Saccharomyces cerevisiae

Abstract

Detoxification and homeostatic acquisition of metal ions are vital for all living organisms. We have identified PCA1 in yeast Saccharomyces cerevisiae as an overexpression suppressor of copper toxicity. PCA1 possesses signatures of a P1B-type heavy metal-transporting ATPase that is widely distributed from bacteria to humans. Copper resistance conferred by PCA1 is not dependent on catalytic activity, but it appears that a cysteine-rich region located in the N terminus sequesters copper. Unexpectedly, when compared with two independent natural isolates and an industrial S. cerevisiae strain, the PCA1 allele of the common have possesses a in a in P1B-type with a that an in a P1B-type ATPase of a the PCA1 allele in yeast is of the allele in yeast that PCA1 is a as as copper and but not PCA1 and to the a metal in yeast by a P1B-type ATPase that is in and of Detoxification and homeostatic acquisition of metal ions are vital for all living organisms. We have identified PCA1 in yeast Saccharomyces cerevisiae as an overexpression suppressor of copper toxicity. PCA1 possesses signatures of a P1B-type heavy metal-transporting ATPase that is widely distributed from bacteria to humans. Copper resistance conferred by PCA1 is not dependent on catalytic activity, but it appears that a cysteine-rich region located in the N terminus sequesters copper. Unexpectedly, when compared with two independent natural isolates and an industrial S. cerevisiae strain, the PCA1 allele of the common have possesses a in a in P1B-type with a that an in a P1B-type ATPase of a the PCA1 allele in yeast is of the allele in yeast that PCA1 is a as as copper and but not PCA1 and to the a metal in yeast by a P1B-type ATPase that is in and of and of homeostatic and of are and from in and are in a of in and and and of a in copper in the to and is a industrial and in and by the of of of metal and in metal in living and of and for of from the have to the of heavy metal P1B-type ATPase of heavy metal that are distributed from bacteria to metal ions as from the S. of of the that in metal in S. P1B-type have identified in as of in and have that two P1B-type and in copper acquisition and in that to in and of metal ions metal have to S. it that in a and to the in S. in Saccharomyces a sequesters S. a in and yeast heavy and of and in and S. to copper but not and the in S. cerevisiae the with in of the in metal of in and in S. cerevisiae in metal the of heavy metal have S. cerevisiae that copper of the yeast of the identified the P1B-type to in copper S. the resistance of a yeast on of to the PCA1 that the and of of PCA1 in metal have that copper resistance is dependent on PCA1 allele in all yeast a in a in of PCA1 allele resistance by an by a of and and from by and by and of copper and all the yeast the on yeast and for of yeast on with the of copper and for of Copper with a yeast on by in and on with copper from yeast on and identified by copper resistance by of the yeast PCA1 from yeast and and of a yeast for of the PCA1 and with a a and an and and of PCA1 by of the and and and and by of a the for of and two natural the PCA1 of the and of by the by with and in with to the for to to in and on a and metal ions to the for in and two in in for and to with for two in and in to the metal by the of of from yeast and as S. by the to the by and to a by a and with and by and and with for and from and on an and and to a with the of with by by Copper in in heavy metal a of S. cerevisiae that of the yeast on copper of two P1B-type in the S. cerevisiae S. of PCA1 resistance in the to copper compared with of PCA1 in the in a in to copper in a strain, copper resistance not overexpression of PCA1 not all of the of the P1B-type ATPase is for heavy metal an metal-transporting is located in the catalytic that the and the PCA1 a heavy located the of PCA1 compared with P1B-type is a the the copper resistance by PCA1 is dependent on ATPase of of of and for copper copper resistance in all that copper resistance is not dependent on metal that the N terminus as copper to the in the of in copper resistance that of by copper ions in a to Copper resistance is of the the of copper in to a in is a S. cerevisiae in of the PCA1 of with natural and that the a in the PCA1 in a of PCA1 from the as as an industrial yeast the to the strain, the PCA1 of yeast S. and the not a common of and P1B-type that is of of the of two P1B-type and an S. S. of is by an in in with with the that S. cerevisiae a of a in PCA1 that in a in region of the of PCA1 from and with the region of P1B-type and S. cerevisiae S. and identified in the and S. cerevisiae from for and with to the of the natural allele and the allele in a yeast and metal of to on a compared with and PCA1 the on with copper is for copper resistance dependent on metal ATPase in when of to not in metal and by natural allele a in resistance to toxicity. PCA1 from a natural of a of the on with the a in resistance of compared with natural and PCA1 with of natural on with resistance conferred by is dependent on P1B-type ATPase catalytic in in the and the the on with of the N terminus of is not for PCA1 and on with the of the a PCA1 it that is to compared with compared the and the is to of in the resistance compared with in to in the with a natural that for of of the PCA1 in the not of of natural on the a the when is that to resistance resistance is with metal of a P1B-type of P1B-type the the and the resistance that resistance is dependent on an metal of PCA1 for a that not have with We the of in resistance by the and a allele allele the it is for resistance the are to and copper compared with of not resistance as compared with that the copper and but it is not for copper resistance conferred by in the the that copper resistance conferred by PCA1 is not dependent on ATPase but metal by in to by of when in as compared with and PCA1 a in that to the that yeast of with of to and on and an on in is in the to an yeast with to in and to in for and in and the that as a resistance is dependent on an overexpression of with PCA1 in with for and and by the of independent with an of of the in with for and on with a in with for and in and the of independent of of PCA1 in the it is to that PCA1 not of the PCA1 the of copper to and copper an for the We the of from to and resistance that not not by a to in a and but copper and the of an for by a and it is that and PCA1 a P1B-type the not by metal ions the that the metal of PCA1 is independent of the not of PCA1 and copper not of in with copper for to of and by of with in with for by as a of with a for in with copper and by as a of of as a that it is the and PCA1 with the N terminus by resistance conferred by and not PCA1 and distributed the with the by and the of as as copper and not to the in with a in is the in the of as as copper and not of and to the on for not of the by it not to the and that the of and a of the that the PCA1 that metal ions and and in of of and with to with for in and by and of from with and by as a ATPase of ions and the of all on for a of are vital for and of P1B-type ATPase as and S. the that of the two P1B-type in the S. cerevisiae is a that is in all yeast that have and of PCA1 the are to of to is a of identified in of and of PCA1 the of and of P1B-type that the S. cerevisiae that have widely as an in not in the living in natural and as a P1B-type ATPase not a the appears to the in copper as for copper of copper in the that in metal of by as for the S. is to that and two P1B-type of a the terminus not with with appears that region is not for of the the not region with with to of and of of in We are the of the of of P1B-type ATPase is the to located the region S. and two a copper in a copper to is by in the and of and have to copper of and S. of the in PCA1 that the two are for to is for PCA1 two but with metal and of the PCA1 metal for metal of of P1B-type that the copper with the metal of and PCA1 from a S. with the PCA1 metal to a as S. are on and the for the is not that PCA1 overexpression and resistance of PCA1 appears to the P1B-type is that PCA1 heavy metal but not by metal We have by the of a PCA1 that is in the of and in ATPase PCA1 of the PCA1 of two independent natural and an industrial identified a to in all a all the is that the S. cerevisiae the to the a PCA1 allele identified in a yeast that on of an in resistance conferred by the PCA1 in it appears that a PCA1 to the allele PCA1 in of a compared with a natural the compared with when PCA1 in the of in of the of in the to a of the in of and of P1B-type have the of of of and to the copper the for in the S. S. of copper of to the and to S. to of of P1B-type have in and bacteria S. S. S. S. PCA1 are not by copper. PCA1 and to the is a of for of copper and PCA1 PCA1 not the N terminus of PCA1 possesses a region that it is that metal to of that the in PCA1 is of and in an of two independent of P1B-type S. S. it is that is in the to a identified in of to in from and metal of PCA1 of We are is of the is from the to to as in and in and as resistance have to S. identified P1B-type in the in to and of in to and for of heavy and of homeostatic and of are and from in and are in a of in and and and of a in copper in the to and is a industrial and in and by the of of of metal and in metal in living and of and for of from the have to the of heavy metal P1B-type ATPase of heavy metal that are distributed from bacteria to metal ions as from the S. of of the that in metal in S. P1B-type have identified in as of in and have that two P1B-type and in copper acquisition and in that to in and of metal ions metal have to S. it that in a and to the in S. in Saccharomyces a sequesters S. a in and yeast heavy and of and in and S. to copper but not and the in S. cerevisiae the with in of the in metal of in and in S. cerevisiae in metal the of heavy metal have S. cerevisiae that copper of the yeast of the identified the P1B-type to in copper S. the resistance of a yeast on of to the PCA1 that the and of of PCA1 in metal have that copper resistance is dependent on PCA1 allele in all yeast a in a in of PCA1 allele resistance by an by a of and and from by and by and of copper and all the yeast the on yeast and for of yeast on with the of copper and for of Copper with a yeast on by in and on with copper from yeast on and identified by copper resistance by of the yeast PCA1 from yeast and and of a yeast for of the PCA1 and with a a and an and and of PCA1 by of the and and and and by of a the for of and two natural the PCA1 of the and of by the by with and in with to the for to to in and on a and metal ions to the for in and two in in for and to with for two in and in to the metal by the of of from yeast and as S. by the to the by and to a by a and with and by and and with for and from and on an and and to a with the of with by by and and from by and by and of copper and all the yeast the on yeast and for of yeast on with the of copper and for of Copper with a yeast on by in and on with copper from yeast on and identified by copper resistance by of the yeast PCA1 from yeast and and of a yeast for of the PCA1 and with a a and an and and of PCA1 by of the and and and and by of a the for of and two natural the PCA1 of the and of by the by with and in with to the for to to in and on a and metal ions to the for in and two in in for and to with for two in and in to the metal by the of of from yeast and as S. by the to the by and to a by a and with and by and and with for and from and on an and and to a with the of with by by Copper in in heavy metal a of S. cerevisiae that of the yeast on copper of two P1B-type in the S. cerevisiae S. of PCA1 resistance in the to copper compared with of PCA1 in the in a in to copper in a strain, copper resistance not overexpression of PCA1 not all of the of the P1B-type ATPase is for heavy metal an metal-transporting is located in the catalytic that the and the PCA1 a heavy located the of PCA1 compared with P1B-type is a the the copper resistance by PCA1 is dependent on ATPase of of of and for copper copper resistance in all that copper resistance is not dependent on metal that the N terminus as copper to the in the of in copper resistance that of by copper ions in a to Copper resistance is of the the of copper in to a in is a S. cerevisiae in of the PCA1 of with natural and that the a in the PCA1 in a of PCA1 from the as as an industrial yeast the to the strain, the PCA1 of yeast S. and the not a common of and P1B-type that is of of the of two P1B-type and an S. S. of is by an in in with with the that S. cerevisiae a of a in PCA1 that in to the of the natural allele and the allele in a yeast and metal of to on a compared with and PCA1 the on with copper is for copper resistance dependent on metal ATPase in when of to not in metal and by natural allele a in resistance to toxicity. 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S. of copper of to the and to S. to of of P1B-type have in and bacteria S. S. S. S. PCA1 are not by copper. PCA1 and to the is a of for of copper and PCA1 PCA1 not the N terminus of PCA1 possesses a region that it is that metal to of that the in PCA1 is of and in an of two independent of P1B-type S. S. it is that is in the to a identified in of to in from and metal of PCA1 of We are is of the is from the to to as in and in and as resistance have to S. identified P1B-type in the in to and of in to and for of heavy ATPase of ions and the of all on for a of are vital for and of P1B-type ATPase as and S. the that of the two P1B-type in the S. cerevisiae is a that is in all yeast that have and of PCA1 the are to of to is a of identified in of and of PCA1 the of and of P1B-type that the S. cerevisiae that have widely as an in not in the living in natural PCA1 and as a P1B-type ATPase not a the appears to the in copper as for copper of copper in the that in metal of by as for the S. is to that and two P1B-type of a the terminus not with with appears that region is not for of the the not region with with to of and of of in We are the of the of of P1B-type ATPase is the to located the region S. and two a copper in a copper to is by in the and of and have to copper of and S. of the in PCA1 that the two are for to is for PCA1 two but with metal and of the PCA1 metal for metal of of P1B-type that the copper with the metal of and PCA1 from a S. with the PCA1 metal to a as S. P1B-type are on and the for the is not that PCA1 overexpression and resistance of PCA1 appears to the P1B-type is that PCA1 heavy metal but not by metal We have by the of a PCA1 that is in the of and in ATPase PCA1 of the PCA1 of two independent natural and an industrial identified a to in all a all the is that the S. cerevisiae the to the a PCA1 allele identified in a yeast that on of an in resistance conferred by the PCA1 in it appears that a PCA1 to the allele PCA1 in of a compared with a natural the compared with when PCA1 in the of in of the of in the to a of the in of and of P1B-type have the of of of and to the copper the for in the S. S. of copper of to the and to S. to of of P1B-type have in and bacteria S. S. S. S. PCA1 are not by copper. PCA1 and to the is a of for of copper and PCA1 PCA1 not the N terminus of PCA1 possesses a region that it is that metal to of that the in PCA1 is of and in an of two independent of P1B-type S. S. it is that is in the to a identified in of to in from and metal of PCA1 of We are is of the is from the to to as in and in and as resistance have to S. identified P1B-type in the in to and of in to and for of heavy We are to the of and for and We for the yeast