HEAT repeat
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), and the yeast kinase TOR1. 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.
| HEAT repeat | |||||||
|---|---|---|---|---|---|---|---|
 An example of an alpha solenoid structure composed of 15 HEAT repeats. The protein phosphatase 2A regulatory subunit is shown with the N-terminus in blue at bottom and the C-terminus in red at top. A single helix-turn-helix motif is shown in the center with the outer helix in pink, the inner helix in green, and the turn in white. From PDB: 2IAE.[1][2] | |||||||
| Identifiers | |||||||
| Symbol | HEAT | ||||||
| Pfam | PF02985 | ||||||
| InterPro | IPR000357 | ||||||
| PROSITE | PDOC50077 | ||||||
| SCOP2 | 1b3u / SCOPe / SUPFAM | ||||||
| |||||||
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),[3] and the yeast kinase TOR1.[4] 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
[edit]Representative examples of HEAT repeat proteins include importin β (also known as karyopherin β) family,[5] regulatory subunits of condensin and cohesin,[6] separase,[7] PIKKs (phosphatidylinositol 3-kinase-related protein kinases) such as ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3 related),[8][9] and the microtubule-binding protein XMAP215/Dis1/TOG[10] and CLASP.[11] Thus, cellular functions of HEAT repeat proteins are highly variable.
The structure of the following HEAT repeat proteins have been determined so far:
- Protein modification and degradation
- Nucleo-cytoplasmic transport
- Transcriptional regulation
- Translational regulation
- Elongation factor eEF3[27]
- Initiation factor eIF4G[28]
- Aminoacyl tRNA synthetase transfer protein Cex1p[29]
- DNA repair
- DNA-PK (DNA-dependent protein kinase)[30]
- Fanconi anemia responsible protein FANCF (FANCF)[31]
- Damaged DNA-binding protein AlkD (Alkylpurin DNA glycosylase)[32]
- PIKKs chaperone Tel2[33]
- Chromosomal regulation
- Cytoskeletal regulation
- Microtubule-binding protein TOG[50][51]/Stu2[52]
- Cell proliferation regulation
- TOR (target of rapamycin)[53]
- Others
References
[edit]- ^ Cho, Uhn Soo; Xu, Wenqing (1 November 2006). "Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme". Nature. 445 (7123): 53–57. doi:10.1038/nature05351. PMID 17086192. S2CID 4408160.
- ^ a b Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D (January 1999). "The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs". Cell. 96 (1): 99–110. doi:10.1016/S0092-8674(00)80963-0. PMID 9989501. S2CID 14465060.
- ^ Kobe, Bostjan; Gleichmann, Thomas; Horne, James; Jennings, Ian G.; Scotney, Pierre D.; Teh, Trazel (1999-05-05). "Turn up the HEAT". Structure. 7 (5): R91–R97. doi:10.1016/S0969-2126(99)80060-4. ISSN 0969-2126. PMID 10378263.
- ^ Andrade MA, Bork P (October 1995). "HEAT repeats in the Huntington's disease protein". Nat. Genet. 11 (2): 115–6. doi:10.1038/ng1095-115. PMID 7550332. S2CID 6911746.
- ^ Malik HS, Eickbush TH, Goldfarb DS (1997). "Evolutionary specialization of the nuclear targeting apparatus". Proc. Natl. Acad. Sci. USA. 94 (25): 13738–13742. Bibcode:1997PNAS...9413738M. doi:10.1073/pnas.94.25.13738. PMC 28376. PMID 9391096.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Neuwald AF, Hirano T (2000). "HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions". Genome Res. 10 (10): 1445–52. doi:10.1101/gr.147400. PMC 310966. PMID 11042144.
- ^ Jäger H, Herzig B, Herzig A, Sticht H, Lehner CF, Heidmann S (2004). "Structure predictions and interaction studies indicate homology of separase N-terminal regulatory domains and Drosophila THR". Cell Cycle. 3 (2): 182–188. doi:10.4161/cc.3.2.605. PMID 14712087.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Perry J, Kleckner N (2003). "The ATRs, ATMs, and TORs are giant HEAT repeat proteins". Cell. 112 (2): 151–155. doi:10.1016/s0092-8674(03)00033-3. PMID 12553904. S2CID 17261901.
- ^ Baretić D, Williams RL (2014). "PIKKs--the solenoid nest where partners and kinases meet". Curr. Opin. Struct. Biol. 29: 134–142. doi:10.1016/j.sbi.2014.11.003. PMID 25460276.
- ^ Ohkura, Hiroyuki; Garcia, Miguel A.; Toda, Takashi (1 November 2001). "Dis1/TOG universal microtubule adaptors - one MAP for all?". Journal of Cell Science. 114 (21): 3805–3812. doi:10.1242/jcs.114.21.3805. PMID 11719547.
- ^ Al-Bassam J, Kim H, Brouhard G, van Oijen A, Harrison SC, Chang F (2010). "CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule". Dev. Cell. 19 (2): 245–258. doi:10.1016/j.devcel.2010.07.016. PMC 3156696. PMID 20708587.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E, Yu JW, Strack S, Jeffrey PD, Shi Y (2006). "Structure of the protein phosphatase 2A holoenzyme". Cell. 127 (6): 1239–1251. doi:10.1016/j.cell.2006.11.033. PMID 17174897. S2CID 18584536.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Cho US, Xu W (2007). "Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme". Nature. 445 (7123): 53–57. Bibcode:2007Natur.445...53C. doi:10.1038/nature05351. PMID 17086192. S2CID 4408160.
- ^ Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N (2004). "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. doi:10.1016/j.cell.2004.10.019. PMID 15537541. S2CID 1606360.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Takagi K, Kim S, Yukii H, Ueno M, Morishita R, Endo Y, Kato K, Tanaka K, Saeki Y, Mizushima T (2012). "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. doi:10.1074/jbc.M112.345876. PMC 3320968. PMID 22334676.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Cingolani G, Petosa C, Weis K, Müller CW (1999). "Structure of importin-beta bound to the IBB domain of importin-alpha". Nature. 399 (6733): 221–229. Bibcode:1999Natur.399..221C. doi:10.1038/20367. PMID 10353244. S2CID 4425840.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Chook YM, Blobel G (1999). "Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp". Nature. 399 (6733): 230–237. doi:10.1038/20375. PMID 10353245. S2CID 4413233.
- ^ Bayliss R, Littlewood T, Stewart M (2000). "Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking". Cell. 102 (1): 99–108. doi:10.1016/s0092-8674(00)00014-3. PMID 10929717. S2CID 17495979.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Matsuura Y, Stewart M (2004). "Structural basis for the assembly of a nuclear export complex". Nature. 432 (7019): 872–877. Bibcode:2004Natur.432..872M. doi:10.1038/nature03144. PMID 15602554. S2CID 4406515.
- ^ Imasaki T, Shimizu T, Hashimoto H, Hidaka Y, Kose S, Imamoto N, Yamada M, Sato M (2007). "Structural basis for substrate recognition and dissociation by human transportin 1". Molecular Cell. 28 (1): 57–67. doi:10.1016/j.molcel.2007.08.006. PMID 17936704.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Montpetit B, Thomsen ND, Helmke KJ, Seeliger MA, Berger JM, Weis K (2011). "A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export". Nature. 472 (7342): 238–242. Bibcode:2011Natur.472..238M. doi:10.1038/nature09862. PMC 3078754. PMID 21441902.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Andersen KR, Onischenko E, Tang JH, Kumar P, Chen JZ, Ulrich A, Liphardt JT, Weis K, Schwartz TU (2013). "Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors". eLife. 11 (2) e00745. doi:10.7554/eLife.00745. PMC 3679522. PMID 23795296.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Stuwe T, Lin DH, Collins LN, Hurt E, Hoelz A (2014). "Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins". Proc. Natl. Acad. Sci. 111 (7): 2530–2535. Bibcode:2014PNAS..111.2530S. doi:10.1073/pnas.1311081111. PMC 3932873. PMID 24505056.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Scheer E, Delbac F, Tora L, Moras D, Romier C (2012). "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. doi:10.1074/jbc.M112.379206. PMC 3431708. PMID 22696218.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Wollmann P, Cui S, Viswanathan R, Berninghausen O, Wells MN, Moldt M, Witte G, Butryn A, Wendler P, Beckmann R, Auble DT, Hopfner KP (2011). "Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP". Nature. 475 (7356): 403–407. doi:10.1038/nature10215. PMC 3276066. PMID 21734658.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Blattner C, Jennebach S, Herzog F, Mayer A, Cheung AC, Witte G, Lorenzen K, Hopfner KP, Heck AJ, Aebersold R, Cramer P (2011). "Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth". Genes Dev. 25 (19): 2093–2105. doi:10.1101/gad.17363311. PMC 3197207. PMID 21940764.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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 (2006). "Structure of eEF3 and the mechanism of transfer RNA release from the E-site". Nature. 443 (7112): 663–668. Bibcode:2006Natur.443..663A. doi:10.1038/nature05126. hdl:11858/00-001M-0000-0010-8377-7. PMID 16929303. S2CID 14994883.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Marcotrigiano J, Lomakin IB, Sonenberg N, Pestova TV, Hellen CU, Burley SK (2001). "A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery". Mol. Cell. 7 (1): 193–203. doi:10.1016/s1097-2765(01)00167-8. PMID 11172724.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Nozawa K, Ishitani R, Yoshihisa T, Sato M, Arisaka F, Kanamaru S, Dohmae N, Mangroo D, Senger B, Becker HD, Nureki O (2013). "Crystal structure of Cex1p reveals the mechanism of tRNA trafficking between nucleus and cytoplasm". Nucleic Acids Res. 41 (6): 3901–3914. doi:10.1093/nar/gkt010. PMC 3616705. PMID 23396276.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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): 118–121. doi:10.1038/nature08648. PMC 2811870. PMID 20023628.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kowal P, Gurtan AM, Stuckert P, D'Andrea AD, Ellenberger T (2007). "Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex". J. Biol. Chem. 282 (3): 2047–2055. doi:10.1074/jbc.M608356200. PMID 17082180.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Rubinson EH, Gowda AS, Spratt TE, Gold B, Eichman BF (2010). "An unprecedented nucleic acid capture mechanism for excision of DNA damage". Nature. 468 (7322): 406–411. Bibcode:2010Natur.468..406R. doi:10.1038/nature09428. PMC 4160814. PMID 20927102.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Takai H, Xie Y, de Lange T, Pavletich NP (2010). "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes". Genes Dev. 24 (18): 2019–2030. doi:10.1101/gad.1956410. PMC 2939364. PMID 20801936.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H (2014). "Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion". Nat. Struct. Mol. Biol. 21 (10): 864–870. doi:10.1038/nsmb.2880. PMC 4190070. PMID 25173175.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Roig MB, Löwe J, Chan KL, Beckouët F, Metson J, Nasmyth K (2014). "Structure and function of cohesin's Scc3/SA regulatory subunit". FEBS Lett. 588 (20): 3692–3702. doi:10.1016/j.febslet.2014.08.015. PMC 4175184. PMID 25171859.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Li Y, Muir K, Bowler MW, Metz J, Haering CH, Panne D (2018). "Structural basis for Scc3-dependent cohesin recruitment to chromatin". eLife. 7: e38356. doi: 10.7554/eLife.38356. doi:10.7554/eLife.38356. PMC 6120753. PMID 30109982.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Chatterjee A, Zakian S, Hu XW, Singleton MR (2013). "Structural insights into the regulation of cohesion establishment by Wpl1". EMBO J. 32 (5): 677–687. doi:10.1038/emboj.2013.16. PMC 3590988. PMID 23395900.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Ouyang Z, Zheng G, Song J, Borek DM, Otwinowski Z, Brautigam CA, Tomchick DR, Rankin S, Yu H (2013). "Structure of the human cohesin inhibitor Wapl". Proc. Natl. Acad. Sci. USA. 110 (28): 11355–11360. Bibcode:2013PNAS..11011355O. doi:10.1073/pnas.1304594110. PMC 3710786. PMID 23776203.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Muir KW, Kschonsak M, Li Y, Metz J, Haering CH, Panne D. (2016). "Structure of the Pds5-Scc1 complex and implications for cohesin function". Cell Rep. 14 (9): 2116–2126. doi:10.1016/j.celrep.2016.01.078. PMID 26923589.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Lee BG, Roig MB, Jansma M, Petela N, Metson J, Nasmyth K, Löwe J (2016). "Crystal structure of the cohesin gatekeeper Pds5 and in complex with kleisin Scc1". Cell Rep. 14 (9): 2108–2115. doi:10.1016/j.celrep.2016.02.020. PMC 4793087. PMID 26923598.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Ouyang Z, Zheng G, Tomchick DR, Luo X, Yu H. (2016). "Structural basis and IP6 requirement for Pds5-dependent cohesin dynamics". Mol Cell. 62 (2): 248–259. doi:10.1016/j.molcel.2016.02.033. PMC 5560056. PMID 26971492.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kikuchi S, Borek DM, Otwinowski Z, Tomchick DR, Yu H (2016). "Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy". Proc Natl Acad Sci USA. 113 (44): 12444–12449. Bibcode:2016PNAS..11312444K. doi:10.1073/pnas.1611333113. PMC 5098657. PMID 27791135.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Chao WC, Murayama Y, Muñoz S, Jones AW, Wade BO, Purkiss AG, Hu XW, Borg A, Snijders AP, Uhlmann F, Singleton MR (2017). "Structure of the cohesin loader Scc2". Nat Commun. 8 13952. Bibcode:2017NatCo...813952C. doi:10.1038/ncomms13952. PMC 5227109. PMID 28059076.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Bachmann G, Richards MW, Winter A, Beuron F, Morris E, Bayliss R (2016). "A closed conformation of the Caenorhabditis elegans separase-securin complex". Open Biol. 6 (4): 160032. doi: 10.1098/rsob.160032. doi:10.1098/rsob.160032. PMC 4852461. PMID 27249343.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Luo S, Tong L (2017). "Molecular mechanism for the regulation of yeast separase by securin". Nature. 542 (7640): 255–259. Bibcode:2017Natur.542..255L. doi:10.1038/nature21061. PMC 5302053. PMID 28146474.
- ^ Boland A, Martin TG, Zhang Z, Yang J, Bai XC, Chang L, Scheres SH, Barford D (2017). "Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution". Nat Struct Mol Biol. 24 (4): 414–418. doi:10.1038/nsmb.3386. PMC 5385133. PMID 28263324.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kschonsak M, Merkel F, Bisht S, Metz J, Rybin V, Hassler M, Haering CH (2017). "Structural basis for a safety-belt mechanism that anchors condensin to chromosomes". Cell. 171 (3): 588–600.e24. doi:10.1016/j.cell.2017.09.008. PMC 5651216. PMID 28988770.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Hara, Kodai; Kinoshita, Kazuhisa; Migita, Tomoko; Murakami, Kei; Shimizu, Kenichiro; Takeuchi, Kozo; Hirano, Tatsuya; Hashimoto, Hiroshi (12 March 2019). "Structural basis of HEAT -kleisin interactions in the human condensin I subcomplex". EMBO Reports. 20 (5). doi:10.15252/embr.201847183. PMC 6501013. PMID 30858338.
- ^ Hassler M, Shaltiel IA, Kschonsak M, Simon B, Merkel F, Thärichen L, Bailey HJ, Macošek J, Bravo S, Metz J, Hennig J, Haering CH (2019). "Structural basis of an asymmetric condensin ATPase cycle". Mol Cell. 74 (6): 1175–1188.e24. doi:10.1016/j.molcel.2019.03.037. PMC 6591010. PMID 31226277.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Al-Bassam J, Larsen NA, Hyman AA, Harrison SC (2007). "Crystal structure of a TOG domain: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding". Structure. 15 (3): 355–362. doi:10.1016/j.str.2007.01.012. PMID 17355870.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Slep KC, Vale RD. (2007). "Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1". Molecular Cell. 27 (6): 976–991. doi:10.1016/j.molcel.2007.07.023. PMC 2052927. PMID 17889670.
- ^ Ayaz P, Ye X, Huddleston P, Brautigam CA, Rice LM. (2012). "A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase". Science. 337 (6096): 857–60. Bibcode:2012Sci...337..857A. doi:10.1126/science.1221698. PMC 3734851. PMID 22904013.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Aylett CH, Sauer E, Imseng S, Boehringer D, Hall MN, Ban N, Maier T (2016). "Architecture of human mTOR complex 1". Science. 351 (6268): 48–52. Bibcode:2016Sci...351...48A. doi:10.1126/science.aaa3870. PMID 26678875. S2CID 32663149.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Han BG, Kim KH, Lee SJ, Jeong KC, Cho JW, Noh KH, Kim TW, Kim SJ, Yoon HJ, Suh SW, Lee S, Lee BI (2012). "Helical repeat structure of apoptosis inhibitor 5 reveals protein-protein interaction modules". J. Biol. Chem. 287 (14): 10727–10737. doi:10.1074/jbc.M111.317594. PMC 3322819. PMID 22334682.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Sagermann M, Stevens TH, Matthews BW (2001). "Crystal structure of the regulatory subunit H of the V-type ATPase of Saccharomyces cerevisiae". Proc. Natl. Acad. Sci. USA. 98 (13): 7134–7139. Bibcode:2001PNAS...98.7134S. doi:10.1073/pnas.131192798. PMC 34635. PMID 11416198.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
[edit]- Eukaryotic Linear Motif resource motif class LIG_PIKK_1
- Eukaryotic Linear Motif resource motif class DOC_PIKK_1