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Universality and Structure of the N-end Rule

Gonda, David K. and Bachmair, Andreas and Wünning, Ingrid and Tobias, John W. and Lane, William S. and Varshavsky, Alexander (1989) Universality and Structure of the N-end Rule. Journal of Biological Chemistry, 264 (28). pp. 16700-16712. ISSN 0021-9258. doi:10.1016/s0021-9258(19)84762-2.

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Our previous work has shown that, in the yeast Saccharomyces cerevisiae, any of the eight stabilizing amino-terminal residues confers a long (> 20 h) half-life on a test protein β-galactosidase (β gal), whereas 12 destabilizing amino-terminal residues confer on β gal half-lives from less than 3 min to 30 min. We now show that an analogous single-residue code (the N-end rule) operates in an in vitro system derived from mammalian reticulocytes. We also show that the N-end rule has a hierarchical structure. Specifically, amino-terminal Glu and Asp (and also Cys in reticulocytes) are secondary destabilizing residues in that they are destabilizing through their ability to be conjugated to primary destabilizing residues such as Arg. Amino-terminal Gln and Asn are tertiary destabilizing residues in that they are destabilizing through their ability to be converted, via selective deamidation, into secondary destabilizing residues Glu and Asp. Furthermore, in reticulocytes, distinct types of the N-end-recognizing activity are shown to be specific for three classes of primary destabilizing residues: basic (Arg, Lys, His), bulky hydrophobic (Phe, Leu, Trp, Tyr), and small uncharged (Ala, Ser, Thr). Features of the N-end rule in reticulocytes suggest that the exact form of the N-end rule may depend on the cell's physiological state, thereby providing a mechanism for selective destruction of preexisting proteins upon cell differentiation.

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Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1990 American Society for Biochemistry and Molecular Biology. Under an Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Received for publication, February 2, 1989. This work was supported in part by Grants GM31530 and DK39520 (to A. V.) from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Fellow of the Jane Coffin Childs Memorial Fund for Medical Research. Fellow of the European Molecular Biology Organization. Fellow of Deutsche Forschungsgemeinschaft. We thank members of this laboratory, especially Bonnie Bartel, Daniel Finley, and Mark Hochstrasser, for their comments on the manuscript, and Barbara Doran for secretarial assistance.
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Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
European Molecular Biology Organization (EMBO)UNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Issue or Number:28
Record Number:CaltechAUTHORS:20210129-142402869
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Official Citation:D K Gonda, A Bachmair, I Wünning, J W Tobias, W S Lane, A Varshavsky, Universality and Structure of the N-end Rule, Journal of Biological Chemistry, Volume 264, Issue 28, 1989, Pages 16700-16712, ISSN 0021-9258, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107818
Deposited By: George Porter
Deposited On:01 Feb 2021 16:04
Last Modified:16 Nov 2021 19:06

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