Advertisement

The Role of Multiple Sequence Repeat Motifs in the Assembly of Multi-protein Complexes

  • David Barford
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)

Abstract

Proteins incorporating multiple sequence repeats (for example ARM, HEAT, TPR, LRR and ankyrin) play critical roles in coordinating the assembly of multi-subunit complexes. This lecture will discuss the different types of protein architecture generated by successive copies of each repeat motif type and describe how these structures are suited to the formation of protein-protein interactions, allowing such proteins to function as scaffolding proteins in the assembly of multi-protein complexes.

Keywords

Leucine Rich Repeat Ankyrin Repeat Tandem Array Heat Repeat Helical Repeat 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Andrade MA, Bork P (1995) HEAT repeats in the Huntington’s disease protein. Nat Genet 11(2):115–116CrossRefGoogle Scholar
  2. 2.
    Barford D (1996) Molecular mechanisms of the protein serine/threonine phosphatases. Trends Biochem Sci 21(11):407–412CrossRefGoogle Scholar
  3. 3.
    Barford D, Das AK, Egloff MP (1998) The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct 27:133–164CrossRefGoogle Scholar
  4. 4.
    Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ, Serrano M, Brenner SL, Blundell TL, Laue ED (1998) Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d. Nature 395(6699):244–250CrossRefADSGoogle Scholar
  5. 5.
    Chook YM, Blobel G (1999) Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp. Nature 399(6733):230–237CrossRefADSGoogle Scholar
  6. 6.
    Conti E, Uy M, Leighton L, Blobel G, Kuriyan J (1998) Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha. Cell 94(2):193–204CrossRefGoogle Scholar
  7. 7.
    D’Andrea LD, Regan L (2003) TPR proteins: the versatile helix. Trends Biochem Sci 28(12):655–662CrossRefGoogle Scholar
  8. 8.
    Das AK, Cohen PW, Barford D (1998) The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions. EMBO J 17(5):1192–1199CrossRefGoogle Scholar
  9. 9.
    Groves MR, Barford D (1999) Topological characteristics of helical repeat proteins. Curr Opin Struct Biol 9(3):383–389CrossRefGoogle Scholar
  10. 10.
    Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D (1999) The structure of the protein phosphatase 2A PR65/a subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. Cell 96(1):99–110CrossRefGoogle Scholar
  11. 11.
    Harper JW, Burton JL, Solomon MJ (2002) The anaphase-promoting complex: it’s not just for mitosis any more. Genes Dev 16(17):2179–2206CrossRefGoogle Scholar
  12. 12.
    Hirano T, Kinoshita N, Morikawa K, Yanagida M (1990) Snap helix with knob and hole: essential repeats in S. pombe nuclear protein nuc2+. Cell 60(2):319–328CrossRefGoogle Scholar
  13. 13.
    Huber AH, Nelson WJ, Weis WI (1997) Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell 90(5):871–882CrossRefGoogle Scholar
  14. 14.
    Huxford T, Huang DB, Malek S, Ghosh G (1998) The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation. Cell 95(6):759–770CrossRefGoogle Scholar
  15. 15.
    Irniger S, Piatti S, Michaelis C, Nasmyth K (1995) Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell 81(2):269–278CrossRefGoogle Scholar
  16. 16.
    Jacobs MD, Harrison SC (1998) Structure of an IkappaBalpha/NF-kappaB complex. Cell 95(6):749–758CrossRefGoogle Scholar
  17. 17.
    Jinek M, Rehwinkel J, Lazarus BD, Izaurralde E, Hanover JA, Conti E (2004) The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha. Nat Struct Mol Biol 11(10):1001–1007CrossRefGoogle Scholar
  18. 18.
    Kajava AV (2002) What curves alpha-solenoids? Evidence for an alpha-helical toroid structure of Rpn1 and Rpn2 proteins of the 26 S proteasome. J Biol Chem 277(51):49791–49798CrossRefGoogle Scholar
  19. 19.
    King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW (1995) A 20 S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81(2):279–288CrossRefGoogle Scholar
  20. 20.
    Kobe B (1996) Leucines on a roll. Nat Struct Biol 3(12):977–980CrossRefGoogle Scholar
  21. 21.
    Kobe B, Deisenhofer J (1993) Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats. Nature 366(6457):751–756CrossRefADSGoogle Scholar
  22. 22.
    Lamb JR, Michaud WA, Sikorski RS, Hieter PA (1994) Cdc16p, Cdc23p And Cdc27p form a complex essential for mitosis. EMBO J 13(18):4321–4328Google Scholar
  23. 23.
    Lee SJ, Matsuura Y, Liu SM, Stewart M (2005) Structural basis for nuclear import complex dissociation by RanGTP. Nature 435(7042):693–696CrossRefADSGoogle Scholar
  24. 24.
    Lupas A, Baumeister W, Hofmann K (1997) A repetitive sequence in subunits of the 26 S proteasome and 20 S cyclosome (anaphase-promoting complex). Trends Biochem Sci 22(6):195–196CrossRefGoogle Scholar
  25. 25.
    Main ER, Xiong Y, Cocco MJ, D’Andrea L, Regan L (2003) Design of stable alpha-helical arrays from an idealized TPR motif. Structure 11(5):497–508CrossRefGoogle Scholar
  26. 26.
    Matsuura Y, Stewart M (2004) Structural basis for the assembly of a nuclear export complex. Nature 432(7019):872–877CrossRefADSGoogle Scholar
  27. 27.
    Peters JM (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7(9):644–656CrossRefGoogle Scholar
  28. 28.
    Pines J (2006) Mitosis: a matter of getting rid of the right protein at the right time. Trends Cell Biol 16(1):55–63CrossRefGoogle Scholar
  29. 29.
    Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP (1998) Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. Nature 395(6699):237–243CrossRefADSGoogle Scholar
  30. 30.
    Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139(3):468–484CrossRefGoogle Scholar
  31. 31.
    Sibanda BL, Chirgadze DY, Blundell TL (2010) Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats. Nature 463(7277):118–121CrossRefADSGoogle Scholar
  32. 32.
    Sikorski RS, Boguski MS, Goebl M, Hieter P (1990) A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60(2):307–317CrossRefGoogle Scholar
  33. 33.
    Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J, Luca FC, Ruderman JV, Hershko A (1995) The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell 6(2):185–197Google Scholar
  34. 34.
    Sullivan M, Morgan DO (2007) Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol 8(11):894–903CrossRefGoogle Scholar
  35. 35.
    Thornton BR, Toczyski DP (2006) Precise destruction: an emerging picture of the APC. Genes Dev 20(22):3069–3078CrossRefGoogle Scholar
  36. 36.
    Tugendreich S, Tomkiel J, Earnshaw W, Hieter P (1995) CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition. Cell 81(2):261–268CrossRefGoogle Scholar
  37. 37.
    Vetter IR, Arndt A, Kutay U, Gorlich D, Wittinghofer A (1999) Structural view of the Ran-importin beta interaction at 2.3 A resolution. Cell 97(5):635–646CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Division of Structural Biology, Chester Beatty LaboratoriesInstitute of Cancer ResearchLondonUK

Personalised recommendations