Structural and Functional Characterization of Sec66p, a New Subunit of the Polypeptide Translocation Apparatus in the Yeast Endoplasmic Reticulum

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 1993 Sep 1

PMID 8257795

Citations 43

Authors

D Feldheim

K Yoshimura

A Admon

R Schekman

Affiliations

Soon will be listed here.

Abstract

SEC66 encodes the 31.5-kDa glycoprotein of the Sec63p complex, an integral endoplasmic reticulum membrane protein complex required for translocation of presecretory proteins in Saccharomyces cerevisiae. DNA sequence analysis of SEC66 predicts a 23-kDa protein with no obvious NH2-terminal signal sequence but with one domain of sufficient length and hydrophobicity to span a lipid bilayer. Antibodies directed against a recombinant form of Sec66p were used to confirm the membrane location of Sec66p and that Sec66p is a glycoprotein of 31.5 kDa. A null mutation in SEC66 renders yeast cells temperature sensitive for growth. sec66 cells accumulate some secretory precursors at a permissive temperature and a variety of precursors at the restrictive temperature. sec66 cells show defects in Sec63p complex formation. Because sec66 cells affect the translocation of some, but not all secretory precursor polypeptides, the role of Sec66p may be to interact with the signal peptide of presecretory proteins.

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References

Struhl K . Nucleotide sequence and transcriptional mapping of the yeast pet56-his3-ded1 gene region. Nucleic Acids Res. 1985; 13(23):8587-601. PMC: 322154. DOI: 10.1093/nar/13.23.8587. View

KYTE J, Doolittle R . A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1):105-32. DOI: 10.1016/0022-2836(82)90515-0. View

Yamamoto T, McIntyre J, Sell S, Georgopoulos C, Skowyra D, Zylicz M . Enzymology of the pre-priming steps in lambda dv DNA replication in vitro. J Biol Chem. 1987; 262(17):7996-9. View

Deshaies R, Schekman R . A yeast mutant defective at an early stage in import of secretory protein precursors into the endoplasmic reticulum. J Cell Biol. 1987; 105(2):633-45. PMC: 2114772. DOI: 10.1083/jcb.105.2.633. View

Huffaker T, Hoyt M, Botstein D . Genetic analysis of the yeast cytoskeleton. Annu Rev Genet. 1987; 21:259-84. DOI: 10.1146/annurev.ge.21.120187.001355. View

Chirico W, Waters M, Blobel G . 70K heat shock related proteins stimulate protein translocation into microsomes. Nature. 1988; 332(6167):805-10. DOI: 10.1038/332805a0. View

Rose M, Misra L, Vogel J . KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene. Cell. 1989; 57(7):1211-21. DOI: 10.1016/0092-8674(89)90058-5. View

Normington K, Kohno K, Kozutsumi Y, Gething M, Sambrook J . S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP. Cell. 1989; 57(7):1223-36. DOI: 10.1016/0092-8674(89)90059-7. View

Hicke L, Schekman R . Yeast Sec23p acts in the cytoplasm to promote protein transport from the endoplasmic reticulum to the Golgi complex in vivo and in vitro. EMBO J. 1989; 8(6):1677-84. PMC: 401009. DOI: 10.1002/j.1460-2075.1989.tb03559.x. View

10.

Rothblatt J, Deshaies R, Sanders S, Daum G, Schekman R . Multiple genes are required for proper insertion of secretory proteins into the endoplasmic reticulum in yeast. J Cell Biol. 1989; 109(6 Pt 1):2641-52. PMC: 2115919. DOI: 10.1083/jcb.109.6.2641. View

11.

Deshaies R, Schekman R . SEC62 encodes a putative membrane protein required for protein translocation into the yeast endoplasmic reticulum. J Cell Biol. 1989; 109(6 Pt 1):2653-64. PMC: 2115948. DOI: 10.1083/jcb.109.6.2653. View

12.

Sadler I, Chiang A, Kurihara T, Rothblatt J, Way J, Silver P . A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to DnaJ, an Escherichia coli heat shock protein. J Cell Biol. 1989; 109(6 Pt 1):2665-75. PMC: 2115965. DOI: 10.1083/jcb.109.6.2665. View

13.

Hann B, Poritz M, Walter P . Saccharomyces cerevisiae and Schizosaccharomyces pombe contain a homologue to the 54-kD subunit of the signal recognition particle that in S. cerevisiae is essential for growth. J Cell Biol. 1989; 109(6 Pt 2):3223-30. PMC: 2115968. DOI: 10.1083/jcb.109.6.3223. View

14.

Vogel J, Misra L, Rose M . Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast. J Cell Biol. 1990; 110(6):1885-95. PMC: 2116122. DOI: 10.1083/jcb.110.6.1885. View

15.

von Heijne G . The signal peptide. J Membr Biol. 1990; 115(3):195-201. DOI: 10.1007/BF01868635. View

16.

Jones J, Prakash L . Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers. Yeast. 1990; 6(5):363-6. DOI: 10.1002/yea.320060502. View

17.

Shen S, Chretien P, Bastien L, Slilaty S . Primary sequence of the glucanase gene from Oerskovia xanthineolytica. Expression and purification of the enzyme from Escherichia coli. J Biol Chem. 1991; 266(2):1058-63. View

18.

Deshaies R, Sanders S, Feldheim D, Schekman R . Assembly of yeast Sec proteins involved in translocation into the endoplasmic reticulum into a membrane-bound multisubunit complex. Nature. 1991; 349(6312):806-8. DOI: 10.1038/349806a0. View

19.

Hann B, Walter P . The signal recognition particle in S. cerevisiae. Cell. 1991; 67(1):131-44. DOI: 10.1016/0092-8674(91)90577-l. View

20.

Green N, Fang H, Walter P . Mutants in three novel complementation groups inhibit membrane protein insertion into and soluble protein translocation across the endoplasmic reticulum membrane of Saccharomyces cerevisiae. J Cell Biol. 1992; 116(3):597-604. PMC: 2289319. DOI: 10.1083/jcb.116.3.597. View