Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2

J. B. Nielsen, F. Foor, John Siekierka, M. J. Hsu, N. Ramadan, N. Morin, A. Shafiee, A. M. Dahl, L. Brizuela, G. Chrebet, K. A. Bostian, S. A. Parent

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Abstract

The immunosuppressants FK506 and rapamycin prevent T-cell activation and also inhibit the growth of certain strains of the yeast Saccharomyces cerevisiae. It has previously been shown that yeast contains a 12-kDa cytosolic FK506-binding protein (yFKBP-12), which also possesses peptidylprolyl cis-trans isomerase activity, and that fkb1 strains lacking yFKBP-12 are resistant to rapamycin and sensitive to FK506. The absence of yFKBP-12 permitted the detection and isolation of a second FK506- and rapamycin-binding protein, which is about 13 kDa in size (yFKBP-13) and membrane-associated. Purified yFKBP-13 binds FK506 with 15-fold lower affinity than yFKBP-12 and has peptidylprolyl cis-trans isomerase activity with a similar substrate profile. The sequence of the first 37 N-terminal amino acids was determined, and the yFKBP-13 gene (FKB2) was cloned and sequenced. A hydrophobic putative signal sequence precedes the N terminus of the mature protein. yFKBP-13 most closely resembles the membrane-associated human FKBP-13, which also possesses a signal peptide, whereas yFKBP-12 most closely resembles human FKBP-12. fkb2 and fkb1 fkb2 mutants are viable and unaltered in their sensitivity to FK506, suggesting that yeast possesses an additional target for this drug. Furthermore, fkb2 null mutations confer no change in rapamycin sensitivity. These findings show that yFKBP-13 and yFKBP- 12 have distinct functions within the cell.

Original languageEnglish
Pages (from-to)7471-7475
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number16
DOIs
StatePublished - 1 Jan 1992

Fingerprint

Tacrolimus Binding Proteins
Tacrolimus
cis-trans-Isomerases
Sirolimus
Yeasts
Peptidylprolyl Isomerase
Membranes
Protein Sorting Signals
Genes
Tacrolimus Binding Protein 1A
Immunosuppressive Agents
Saccharomyces cerevisiae
T-Lymphocytes
Amino Acids
Mutation
FKBP-13
Growth
Pharmaceutical Preparations
Proteins

Keywords

  • Saccharomyces cerevisiae
  • immunosuppressant
  • peptidylprolyl cis-trans isomerase
  • rapamycin
  • rotamase

Cite this

Nielsen, J. B. ; Foor, F. ; Siekierka, John ; Hsu, M. J. ; Ramadan, N. ; Morin, N. ; Shafiee, A. ; Dahl, A. M. ; Brizuela, L. ; Chrebet, G. ; Bostian, K. A. ; Parent, S. A. / Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 16. pp. 7471-7475.
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abstract = "The immunosuppressants FK506 and rapamycin prevent T-cell activation and also inhibit the growth of certain strains of the yeast Saccharomyces cerevisiae. It has previously been shown that yeast contains a 12-kDa cytosolic FK506-binding protein (yFKBP-12), which also possesses peptidylprolyl cis-trans isomerase activity, and that fkb1 strains lacking yFKBP-12 are resistant to rapamycin and sensitive to FK506. The absence of yFKBP-12 permitted the detection and isolation of a second FK506- and rapamycin-binding protein, which is about 13 kDa in size (yFKBP-13) and membrane-associated. Purified yFKBP-13 binds FK506 with 15-fold lower affinity than yFKBP-12 and has peptidylprolyl cis-trans isomerase activity with a similar substrate profile. The sequence of the first 37 N-terminal amino acids was determined, and the yFKBP-13 gene (FKB2) was cloned and sequenced. A hydrophobic putative signal sequence precedes the N terminus of the mature protein. yFKBP-13 most closely resembles the membrane-associated human FKBP-13, which also possesses a signal peptide, whereas yFKBP-12 most closely resembles human FKBP-12. fkb2 and fkb1 fkb2 mutants are viable and unaltered in their sensitivity to FK506, suggesting that yeast possesses an additional target for this drug. Furthermore, fkb2 null mutations confer no change in rapamycin sensitivity. These findings show that yFKBP-13 and yFKBP- 12 have distinct functions within the cell.",
keywords = "Saccharomyces cerevisiae, immunosuppressant, peptidylprolyl cis-trans isomerase, rapamycin, rotamase",
author = "Nielsen, {J. B.} and F. Foor and John Siekierka and Hsu, {M. J.} and N. Ramadan and N. Morin and A. Shafiee and Dahl, {A. M.} and L. Brizuela and G. Chrebet and Bostian, {K. A.} and Parent, {S. A.}",
year = "1992",
month = "1",
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doi = "10.1073/pnas.89.16.7471",
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Nielsen, JB, Foor, F, Siekierka, J, Hsu, MJ, Ramadan, N, Morin, N, Shafiee, A, Dahl, AM, Brizuela, L, Chrebet, G, Bostian, KA & Parent, SA 1992, 'Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 16, pp. 7471-7475. https://doi.org/10.1073/pnas.89.16.7471

Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2. / Nielsen, J. B.; Foor, F.; Siekierka, John; Hsu, M. J.; Ramadan, N.; Morin, N.; Shafiee, A.; Dahl, A. M.; Brizuela, L.; Chrebet, G.; Bostian, K. A.; Parent, S. A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 16, 01.01.1992, p. 7471-7475.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the nonessential gene FKB2

AU - Nielsen, J. B.

AU - Foor, F.

AU - Siekierka, John

AU - Hsu, M. J.

AU - Ramadan, N.

AU - Morin, N.

AU - Shafiee, A.

AU - Dahl, A. M.

AU - Brizuela, L.

AU - Chrebet, G.

AU - Bostian, K. A.

AU - Parent, S. A.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - The immunosuppressants FK506 and rapamycin prevent T-cell activation and also inhibit the growth of certain strains of the yeast Saccharomyces cerevisiae. It has previously been shown that yeast contains a 12-kDa cytosolic FK506-binding protein (yFKBP-12), which also possesses peptidylprolyl cis-trans isomerase activity, and that fkb1 strains lacking yFKBP-12 are resistant to rapamycin and sensitive to FK506. The absence of yFKBP-12 permitted the detection and isolation of a second FK506- and rapamycin-binding protein, which is about 13 kDa in size (yFKBP-13) and membrane-associated. Purified yFKBP-13 binds FK506 with 15-fold lower affinity than yFKBP-12 and has peptidylprolyl cis-trans isomerase activity with a similar substrate profile. The sequence of the first 37 N-terminal amino acids was determined, and the yFKBP-13 gene (FKB2) was cloned and sequenced. A hydrophobic putative signal sequence precedes the N terminus of the mature protein. yFKBP-13 most closely resembles the membrane-associated human FKBP-13, which also possesses a signal peptide, whereas yFKBP-12 most closely resembles human FKBP-12. fkb2 and fkb1 fkb2 mutants are viable and unaltered in their sensitivity to FK506, suggesting that yeast possesses an additional target for this drug. Furthermore, fkb2 null mutations confer no change in rapamycin sensitivity. These findings show that yFKBP-13 and yFKBP- 12 have distinct functions within the cell.

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KW - immunosuppressant

KW - peptidylprolyl cis-trans isomerase

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