HEAT repeat explained

A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" is an acronym for four proteins in which this repeat structure is found: Huntingtin, elongation factor 3 (EF3), protein phosphatase 2A (PP2A),[1] and the yeast kinase TOR1.[2] HEAT repeats form extended superhelical structures which are often involved in intracellular transport; they are structurally related to armadillo repeats. The nuclear transport protein importin beta contains 19 HEAT repeats.

Various HEAT repeat proteins and their structures

Representative examples of HEAT repeat proteins include importin β (also known as karyopherin β) family,[3] regulatory subunits of condensin and cohesin,[4] separase,[5] PIKKs (phosphatidylinositol 3-kinase-related protein kinases) such as ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3 related),[6] [7] and the microtubule-binding protein XMAP215/Dis1/TOG[8] and CLASP.[9] Thus, cellular functions of HEAT repeat proteins are highly variable.

The structure of the following HEAT repeat proteins have been determined so far:

Notes and References

  1. Kobe. Bostjan. Gleichmann. Thomas. Horne. James. Jennings. Ian G.. Scotney. Pierre D.. Teh. Trazel. 1999-05-05. Turn up the HEAT. Structure. English. 7. 5. R91–R97. 10.1016/S0969-2126(99)80060-4. 0969-2126. 10378263. free.
  2. Andrade MA, Bork P . HEAT repeats in the Huntington's disease protein . Nat. Genet. . 11 . 2 . 115–6 . October 1995 . 7550332 . 10.1038/ng1095-115 . 6911746 .
  3. Malik HS, Eickbush TH, Goldfarb DS . Evolutionary specialization of the nuclear targeting apparatus . Proc. Natl. Acad. Sci. USA. 94 . 25 . 13738–13742 . 1997 . 10.1073/pnas.94.25.13738 . 9391096. 28376 . 1997PNAS...9413738M . free .
  4. Neuwald AF, Hirano T . HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions . Genome Res.. 10 . 10 . 1445–52 . 2000 . 10.1101/gr.147400 . 11042144. 310966 .
  5. Jäger H, Herzig B, Herzig A, Sticht H, Lehner CF, Heidmann S . Structure predictions and interaction studies indicate homology of separase N-terminal regulatory domains and Drosophila THR . Cell Cycle . 3 . 2 . 182–188 . 2004 . 10.4161/cc.3.2.605 . 14712087. free .
  6. Perry J, Kleckner N . The ATRs, ATMs, and TORs are giant HEAT repeat proteins . Cell. 112 . 2 . 151–155 . 2003 . 10.1016/s0092-8674(03)00033-3 . 12553904. 17261901 . free .
  7. Baretić D, Williams RL . PIKKs--the solenoid nest where partners and kinases meet . Curr. Opin. Struct. Biol. . 29 . 134–142 . 2014 . 10.1016/j.sbi.2014.11.003 . 25460276.
  8. Ohkura . Hiroyuki . Garcia . Miguel A. . Toda . Takashi . Dis1/TOG universal microtubule adaptors - one MAP for all? . Journal of Cell Science . 1 November 2001 . 114 . 21 . 3805–3812 . 10.1242/jcs.114.21.3805 . 11719547 .
  9. Al-Bassam J, Kim H, Brouhard G, van Oijen A, Harrison SC, Chang F . CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule . Dev. Cell. 19 . 2 . 245–258 . 2010 . 10.1016/j.devcel.2010.07.016 . 20708587. 3156696 .
  10. Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D . The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs . Cell . 96 . 1 . 99–110 . January 1999 . 9989501 . 10.1016/S0092-8674(00)80963-0. 14465060 . free .
  11. Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E, Yu JW, Strack S, Jeffrey PD, Shi Y . Structure of the protein phosphatase 2A holoenzyme . Cell. 127 . 6 . 1239–1251 . 2006 . 10.1016/j.cell.2006.11.033 . 17174897. 18584536 . free .
  12. Cho US, Xu W . Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme . Nature. 445. 7123 . 53–57 . 2007 . 10.1038/nature05351 . 17086192 . 2007Natur.445...53C . 4408160 .
  13. Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N . Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases . Cell . 119 . 4 . 517–528 . 2004 . 10.1016/j.cell.2004.10.019 . 15537541. 1606360 . free .
  14. Takagi K, Kim S, Yukii H, Ueno M, Morishita R, Endo Y, Kato K, Tanaka K, Saeki Y, Mizushima T . Structural basis for specific recognition of Rpt1p, an ATPase subunit of 26 S proteasome, by proteasome-dedicated chaperone Hsm3p . J. Biol. Chem. . 287 . 15 . 12172–12182 . 2012 . 10.1074/jbc.M112.345876 . 22334676. 3320968 . free .
  15. Cingolani G, Petosa C, Weis K, Müller CW . Structure of importin-beta bound to the IBB domain of importin-alpha . Nature . 399 . 6733 . 221–229 . 1999. 10353244 . 10.1038/20367. 1999Natur.399..221C . 4425840 .
  16. Chook YM, Blobel G . Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp . Nature. 399 . 6733 . 230–237 . 1999 . 10.1038/20375 . 10353245. 4413233 .
  17. Bayliss R, Littlewood T, Stewart M . Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking . Cell. 102 . 1 . 99–108 . 2000 . 10.1016/s0092-8674(00)00014-3 . 10929717. 17495979 . free .
  18. Matsuura Y, Stewart M . Structural basis for the assembly of a nuclear export complex . Nature. 432 . 7019 . 872–877 . 2004 . 10.1038/nature03144 . 15602554. 2004Natur.432..872M . 4406515 .
  19. Imasaki T, Shimizu T, Hashimoto H, Hidaka Y, Kose S, Imamoto N, Yamada M, Sato M . Structural basis for substrate recognition and dissociation by human transportin 1. Molecular Cell. 28 . 1 . 57–67 . 2007 . 10.1016/j.molcel.2007.08.006. 17936704. free .
  20. Montpetit B, Thomsen ND, Helmke KJ, Seeliger MA, Berger JM, Weis K . A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export . Nature . 472 . 7342 . 238–242 . 2011 . 10.1038/nature09862 . 21441902. 3078754 . 2011Natur.472..238M .
  21. Andersen KR, Onischenko E, Tang JH, Kumar P, Chen JZ, Ulrich A, Liphardt JT, Weis K, Schwartz TU . Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors . eLife . 11 . 2 . e00745 . 2013 . 10.7554/eLife.00745 . 23795296. 3679522 . free .
  22. Stuwe T, Lin DH, Collins LN, Hurt E, Hoelz A. Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins . Proc. Natl. Acad. Sci. . 111 . 7 . 2530–2535 . 2014 . 10.1073/pnas.1311081111 . 24505056. 3932873 . 2014PNAS..111.2530S . free .
  23. Scheer E, Delbac F, Tora L, Moras D, Romier C. TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein . J. Biol. Chem. . 287 . 33 . 27580–27592 . 2012 . 10.1074/jbc.M112.379206 . 22696218. 3431708 . free .
  24. Wollmann P, Cui S, Viswanathan R, Berninghausen O, Wells MN, Moldt M, Witte G, Butryn A, Wendler P, Beckmann R, Auble DT, Hopfner KP . Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP . Nature . 475 . 7356 . 403–407 . 2011 . 10.1038/nature10215 . 21734658. 3276066 .
  25. Blattner C, Jennebach S, Herzog F, Mayer A, Cheung AC, Witte G, Lorenzen K, Hopfner KP, Heck AJ, Aebersold R, Cramer P . Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth . Genes Dev. . 25 . 19 . 2093–2105 . 2011 . 10.1101/gad.17363311 . 21940764. 3197207 .
  26. Andersen CB, Becker T, Blau M, Anand M, Halic M, Balar B, Mielke T, Boesen T, Pedersen JS, Spahn CM, Kinzy TG, Andersen GR, Beckmann R . Structure of eEF3 and the mechanism of transfer RNA release from the E-site . Nature . 443 . 7112 . 663–668 . 2006 . 10.1038/nature05126 . 16929303. 2006Natur.443..663A . 11858/00-001M-0000-0010-8377-7 . 14994883 . free .
  27. Marcotrigiano J, Lomakin IB, Sonenberg N, Pestova TV, Hellen CU, Burley SK . A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery . Mol. Cell . 7 . 1 . 193–203 . 2001 . 10.1016/s1097-2765(01)00167-8 . 11172724. free .
  28. Nozawa K, Ishitani R, Yoshihisa T, Sato M, Arisaka F, Kanamaru S, Dohmae N, Mangroo D, Senger B, Becker HD, Nureki O . Crystal structure of Cex1p reveals the mechanism of tRNA trafficking between nucleus and cytoplasm . Nucleic Acids Res. . 41 . 6 . 3901–3914 . 2013 . 10.1093/nar/gkt010 . 23396276. 3616705 .
  29. Sibanda BL, Chirgadze DY, Blundell TL . Crystal structure of DNA-PKcs reveals a large open-ring cradle HEAT repeats . Nature . 463 . 7277 . 118–121 . 2010 . 10.1038/nature08648 . 20023628. 2811870 .
  30. Kowal P, Gurtan AM, Stuckert P, D'Andrea AD, Ellenberger T . Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex . J. Biol. Chem. . 282 . 3 . 2047–2055 . 2007 . 10.1074/jbc.M608356200 . 17082180. free .
  31. Rubinson EH, Gowda AS, Spratt TE, Gold B, Eichman BF . An unprecedented nucleic acid capture mechanism for excision of DNA damage . Nature . 468 . 7322 . 406–411 . 2010 . 10.1038/nature09428 . 20927102. 4160814 . 2010Natur.468..406R .
  32. Takai H, Xie Y, de Lange T, Pavletich NP . Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes . Genes Dev. . 24 . 18 . 2019–2030 . 2010 . 10.1101/gad.1956410 . 20801936. 2939364 .
  33. Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H . Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion . Nat. Struct. Mol. Biol.. 21 . 10 . 864–870 . 2014. 10.1038/nsmb.2880 . 25173175. 4190070 .
  34. Roig MB, Löwe J, Chan KL, Beckouët F, Metson J, Nasmyth K . Structure and function of cohesin's Scc3/SA regulatory subunit. . FEBS Lett . 588 . 20 . 3692–3702 . 2014. 10.1016/j.febslet.2014.08.015 . 25171859. 4175184 .
  35. Li Y, Muir K, Bowler MW, Metz J, Haering CH, Panne D . Structural basis for Scc3-dependent cohesin recruitment to chromatin. . eLife . 7 . e38356. doi: 10.7554/eLife.38356 . 2018. 10.7554/eLife.38356 . 30109982. 6120753 . free .
  36. Chatterjee A, Zakian S, Hu XW, Singleton MR . Structural insights into the regulation of cohesion establishment by Wpl1 . EMBO J. . 32 . 5 . 677–687 . 2013 . 10.1038/emboj.2013.16 . 23395900. 3590988 .
  37. Ouyang Z, Zheng G, Song J, Borek DM, Otwinowski Z, Brautigam CA, Tomchick DR, Rankin S, Yu H . Structure of the human cohesin inhibitor Wapl . Proc. Natl. Acad. Sci. USA. 110 . 28 . 11355–11360 . 2013 . 10.1073/pnas.1304594110 . 23776203. 3710786 . 2013PNAS..11011355O . free .
  38. Muir KW, Kschonsak M, Li Y, Metz J, Haering CH, Panne D. . Structure of the Pds5-Scc1 complex and implications for cohesin function . Cell Rep. 2016 . 14 . 9 . 2116–2126 . 10.1016/j.celrep.2016.01.078 . 26923589. free .
  39. Lee BG, Roig MB, Jansma M, Petela N, Metson J, Nasmyth K, Löwe J . Crystal structure of the cohesin gatekeeper Pds5 and in complex with kleisin Scc1 . Cell Rep. 2016 . 14 . 9 . 2108–2115 . 10.1016/j.celrep.2016.02.020 . 26923598. 4793087 .
  40. Ouyang Z, Zheng G, Tomchick DR, Luo X, Yu H. . Structural basis and IP6 requirement for Pds5-dependent cohesin dynamics . Mol Cell. 62 . 2 . 248–259 . 2016 . 10.1016/j.molcel.2016.02.033 . 26971492. 5560056 .
  41. Kikuchi S, Borek DM, Otwinowski Z, Tomchick DR, Yu H . Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy. Proc Natl Acad Sci USA. 113 . 44 . 12444–12449 . 2016 . 10.1073/pnas.1611333113. 27791135. 5098657. 2016PNAS..11312444K. free.
  42. Chao WC, Murayama Y, Muñoz S, Jones AW, Wade BO, Purkiss AG, Hu XW, Borg A, Snijders AP, Uhlmann F, Singleton MR . Structure of the cohesin loader Scc2. Nat Commun. 8 . 13952 . 2017 . 10.1038/ncomms13952. 28059076. 5227109. 2017NatCo...813952C.
  43. Bachmann G, Richards MW, Winter A, Beuron F, Morris E, Bayliss R. A closed conformation of the Caenorhabditis elegans separase-securin complex . Open Biol . 6 . 4 . 160032. doi: 10.1098/rsob.160032 . 2016 . 10.1098/rsob.160032 . 27249343. 4852461 .
  44. Luo S, Tong L . Molecular mechanism for the regulation of yeast separase by securin . Nature . 542 . 7640 . 255–259 . 2017 . 10.1038/nature21061 . 28146474. 5302053 . 2017Natur.542..255L .
  45. Boland A, Martin TG, Zhang Z, Yang J, Bai XC, Chang L, Scheres SH, Barford D . Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution . Nat Struct Mol Biol . 24 . 4 . 414–418 . 2017 . 10.1038/nsmb.3386 . 28263324. 5385133 .
  46. Kschonsak M, Merkel F, Bisht S, Metz J, Rybin V, Hassler M, Haering CH. Structural basis for a safety-belt mechanism that anchors condensin to chromosomes . Cell . 171 . 3 . 588–600.e24 . 2017 . 10.1016/j.cell.2017.09.008 . 28988770. 5651216 .
  47. Hara . Kodai . Kinoshita . Kazuhisa . Migita . Tomoko . Murakami . Kei . Shimizu . Kenichiro . Takeuchi . Kozo . Hirano . Tatsuya . Hashimoto . Hiroshi . Structural basis of HEAT -kleisin interactions in the human condensin I subcomplex . EMBO Reports . 12 March 2019 . 20 . 5 . 10.15252/embr.201847183 . 30858338 . 6501013 .
  48. Hassler M, Shaltiel IA, Kschonsak M, Simon B, Merkel F, Thärichen L, Bailey HJ, Macošek J, Bravo S, Metz J, Hennig J, Haering CH. Structural basis of an asymmetric condensin ATPase cycle . Mol Cell . 74 . 6 . 1175–1188.e24 . 2019 . 10.1016/j.molcel.2019.03.037 . 31226277. 6591010 .
  49. Al-Bassam J, Larsen NA, Hyman AA, Harrison SC . Crystal structure of a TOG domain: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding. . Structure. 15 . 3 . 355–362 . 2007 . 10.1016/j.str.2007.01.012 . 17355870. free .
  50. Slep KC, Vale RD. . Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1 . Molecular Cell. 27 . 6 . 976–991 . 2007 . 10.1016/j.molcel.2007.07.023 . 17889670. 2052927 .
  51. Ayaz P, Ye X, Huddleston P, Brautigam CA, Rice LM. . A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase. . Science . 337 . 6096 . 857–60 . 2012 . 10.1126/science.1221698 . 22904013. 3734851 . 2012Sci...337..857A .
  52. Aylett CH, Sauer E, Imseng S, Boehringer D, Hall MN, Ban N, Maier T . Architecture of human mTOR complex 1 . Science . 351 . 6268 . 48–52 . 2016 . 10.1126/science.aaa3870 . 26678875. 2016Sci...351...48A . 32663149 .
  53. Han BG, Kim KH, Lee SJ, Jeong KC, Cho JW, Noh KH, Kim TW, Kim SJ, Yoon HJ, Suh SW, Lee S, Lee BI . Helical repeat structure of apoptosis inhibitor 5 reveals protein-protein interaction modules . J. Biol. Chem. . 287 . 14 . 10727–10737 . 2012 . 10.1074/jbc.M111.317594 . 22334682. 3322819 . free .
  54. Sagermann M, Stevens TH, Matthews BW . Crystal structure of the regulatory subunit H of the V-type ATPase of Saccharomyces cerevisiae . Proc. Natl. Acad. Sci. USA . 98 . 13 . 7134–7139 . 2001 . 10.1073/pnas.131192798 . 11416198. 34635 . 2001PNAS...98.7134S . free .

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