DNA-damage-inducible 1 Protein (Ddi1) Contains an Uncharacteristic Ubiquitin-like Domain That Binds Ubiquitin

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2015 Feb 24

PMID 25703377

Citations 36

Authors

Urszula Nowicka

Daoning Zhang

Olivier Walker

Daria Krutauz

Carlos A Castaneda

Apurva Chaturvedi

Tony Y Chen

Noa Reis

Michael H Glickman

David Fushman

Affiliations

Soon will be listed here.

Abstract

Ddi1 belongs to a family of shuttle proteins targeting polyubiquitinated substrates for proteasomal degradation. Unlike the other proteasomal shuttles, Rad23 and Dsk2, Ddi1 remains an enigma: its function is not fully understood and structural properties are poorly characterized. We determined the structure and binding properties of the ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of Ddi1 from Saccharomyces cerevisiae. We found that while Ddi1UBA forms a characteristic UBA:ubiquitin complex, Ddi1UBL has entirely uncharacteristic binding preferences. Despite having a ubiquitin-like fold, Ddi1UBL does not interact with typical UBL receptors but unexpectedly binds ubiquitin, forming a unique interface mediated by hydrophobic contacts and by salt bridges between oppositely charged residues of Ddi1UBL and ubiquitin. In stark contrast to ubiquitin and other UBLs, the β-sheet surface of Ddi1UBL is negatively charged and therefore is recognized in a completely different way. The dual functionality of Ddi1UBL, capable of binding both ubiquitin and proteasome, suggests an intriguing mechanism for Ddi1 as a proteasomal shuttle.

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References

Trempe J, Brown N, Lowe E, Gordon C, Campbell I, Noble M . Mechanism of Lys48-linked polyubiquitin chain recognition by the Mud1 UBA domain. EMBO J. 2005; 24(18):3178-89. PMC: 1224687. DOI: 10.1038/sj.emboj.7600797. View

Cornilescu G, Delaglio F, Bax A . Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR. 1999; 13(3):289-302. DOI: 10.1023/a:1008392405740. View

Yamaguchi R, Dutta A . Proteasome inhibitors alter the orderly progression of DNA synthesis during S-phase in HeLa cells and lead to rereplication of DNA. Exp Cell Res. 2000; 261(1):271-83. DOI: 10.1006/excr.2000.5053. View

Kaplun L, Ivantsiv Y, Bakhrat A, Raveh D . DNA damage response-mediated degradation of Ho endonuclease via the ubiquitin system involves its nuclear export. J Biol Chem. 2003; 278(49):48727-34. DOI: 10.1074/jbc.M308671200. View

Kaplun L, Tzirkin R, Bakhrat A, Shabek N, Ivantsiv Y, Raveh D . The DNA damage-inducible UbL-UbA protein Ddi1 participates in Mec1-mediated degradation of Ho endonuclease. Mol Cell Biol. 2005; 25(13):5355-62. PMC: 1156969. DOI: 10.1128/MCB.25.13.5355-5362.2005. View

Chen L, Madura K . Rad23 promotes the targeting of proteolytic substrates to the proteasome. Mol Cell Biol. 2002; 22(13):4902-13. PMC: 133919. DOI: 10.1128/MCB.22.13.4902-4913.2002. View

Rao H, Sastry A . Recognition of specific ubiquitin conjugates is important for the proteolytic functions of the ubiquitin-associated domain proteins Dsk2 and Rad23. J Biol Chem. 2002; 277(14):11691-5. DOI: 10.1074/jbc.M200245200. View

Elsasser S, Chandler-Militello D, Muller B, Hanna J, Finley D . Rad23 and Rpn10 serve as alternative ubiquitin receptors for the proteasome. J Biol Chem. 2004; 279(26):26817-22. DOI: 10.1074/jbc.M404020200. View

Ryu K, Lee K, Bae S, Kim B, Kim K, Choi B . Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a. J Biol Chem. 2003; 278(38):36621-7. DOI: 10.1074/jbc.M304628200. View

10.

Heessen S, Masucci M, Dantuma N . The UBA2 domain functions as an intrinsic stabilization signal that protects Rad23 from proteasomal degradation. Mol Cell. 2005; 18(2):225-35. DOI: 10.1016/j.molcel.2005.03.015. View

11.

Gabriely G, Kama R, Gelin-Licht R, Gerst J . Different domains of the UBL-UBA ubiquitin receptor, Ddi1/Vsm1, are involved in its multiple cellular roles. Mol Biol Cell. 2008; 19(9):3625-37. PMC: 2526698. DOI: 10.1091/mbc.e07-05-0462. View

12.

Raasi S, Varadan R, Fushman D, Pickart C . Diverse polyubiquitin interaction properties of ubiquitin-associated domains. Nat Struct Mol Biol. 2005; 12(8):708-14. DOI: 10.1038/nsmb962. View

13.

Ciechanover A . The ubiquitin-mediated proteolytic pathway: mechanisms of action and cellular physiology. Biol Chem Hoppe Seyler. 1994; 375(9):565-81. DOI: 10.1515/bchm3.1994.375.9.565. View

14.

Beal R, Deveraux Q, Xia G, Rechsteiner M, Pickart C . Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting. Proc Natl Acad Sci U S A. 1996; 93(2):861-6. PMC: 40148. DOI: 10.1073/pnas.93.2.861. View

15.

Baranes-Bachar K, Baranes-Bacher K, Khalaila I, Ivantsiv Y, Lavut A, Voloshin O . New interacting partners of the F-box protein Ufo1 of yeast. Yeast. 2008; 25(10):733-43. DOI: 10.1002/yea.1615. View

16.

Singh R, Zerath S, Kleifeld O, Scheffner M, Glickman M, Fushman D . Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system. Mol Cell Proteomics. 2012; 11(12):1595-611. PMC: 3518131. DOI: 10.1074/mcp.M112.022467. View

17.

Ohno A, Jee J, Fujiwara K, Tenno T, Goda N, Tochio H . Structure of the UBA domain of Dsk2p in complex with ubiquitin molecular determinants for ubiquitin recognition. Structure. 2005; 13(4):521-32. DOI: 10.1016/j.str.2005.01.011. View

18.

Kaiser S, Riley B, Shaler T, Trevino R, Becker C, Schulman H . Protein standard absolute quantification (PSAQ) method for the measurement of cellular ubiquitin pools. Nat Methods. 2011; 8(8):691-6. PMC: 3196335. DOI: 10.1038/nmeth.1649. View

19.

Liu Z, Zhang W, Xing Q, Ren X, Liu M, Tang C . Noncovalent dimerization of ubiquitin. Angew Chem Int Ed Engl. 2011; 51(2):469-72. PMC: 3303887. DOI: 10.1002/anie.201106190. View

20.

Koradi R, Billeter M, Wuthrich K . MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph. 1996; 14(1):51-5, 29-32. DOI: 10.1016/0263-7855(96)00009-4. View