Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting - PubMed (original) (raw)

Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting

R Beal et al. Proc Natl Acad Sci U S A. 1996.

Abstract

Ubiquitin conjugation is a signal for degradation of eukaryotic proteins by the 26S protease. Conjugation of a homopolymeric multiubiquitin chain to a substrate lysine residue results in 10-fold faster degradation than does conjugation of monoubiquitin, but the molecular basis of enhanced targeting by chains is unknown. We show that ubiquitin residues L8, I44, and V70 are critical for targeting. Mutation of pairs of these residues to alanine had little effect on attachment of ubiquitin to substrates but severely inhibited degradation of the resulting conjugates. The same mutations blocked the binding of chains to a specific subunit (S5a) of the regulatory complex of the 26S protease. The side chains implicated in this binding--L8, I44, and V70--form repeating patches on the chain surface. Thus, hydrophobic interactions between these patches and S5a apparently contribute to enhanced proteolytic targeting by multiubiquitin chains.

PubMed Disclaimer

References

    1. Cell. 1984 May;37(1):57-66 - PubMed
    1. J Biol Chem. 1992 Jul 15;267(20):14418-23 - PubMed
    1. Mol Cell Biol. 1994 Aug;14(8):5501-9 - PubMed
    1. J Biol Chem. 1986 Feb 15;261(5):2391-9 - PubMed
    1. EMBO J. 1991 Aug;10(8):2187-93 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources