Journal of Biological Chemistry
Volume 276, Issue 32, 10 August 2001, Pages 30483-30489
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PROTEIN SYNTHESIS POST-TRANSLATION MODIFICATION AND DEGRADATION
Distinct Functional Surface Regions on Ubiquitin*

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The characterized functions of the highly conserved polypeptide ubiquitin are to target proteins for proteasome degradation or endocytosis. The formation of a polyubiquitin chain of at least four units is required for efficient proteasome binding. By contrast, monoubiquitin serves as a signal for the endocytosis of plasma membrane proteins. We have defined surface residues that are important for ubiquitin's vital functions inSaccharomyces cerevisiae. Surprisingly, alanine scanning mutagenesis showed that only 16 of ubiquitin's 63 surface residues are essential for vegetative growth in yeast. Most of the essential residues localize to two hydrophobic clusters that participate in proteasome recognition and/or endocytosis. The others reside in or near the tail region, which is important for conjugation and deubiquitination. We also demonstrate that the essential residues comprise two distinct functional surfaces: residues surrounding Phe4 are required for endocytosis, whereas residues surrounding Ile44 are required for both endocytosis and proteasome degradation.

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Published, JBC Papers in Press, June 8, 2001, DOI 10.1074/jbc.M103248200

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This work was supported by National Institutes of Health Grants DK46984 (to C. P.) and DK53257 (to L. H.), the Burroughs Wellcome Foundation, and the Searle Scholars Program.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Present address: Cancer Research Laboratories, The Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, QLD 4029, Australia.

To whom correspondence may be addressed: Dept. of Biochemistry and Molecular Biology, School of Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205. E-mail: [email protected].

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To whom correspondence may be addressed. Tel.: 847-467-4490; Fax: 847-467-1380; E-mail: [email protected].