3q9p Citations

Three-dimensional structure of α-crystallin domain dimers of human small heat shock proteins HSPB1 and HSPB6.

J. Mol. Biol. 411 110-22 (2011)
Cited: 47 times
EuropePMC logo PMID: 21641913


Small heat shock proteins (sHSPs) are a family of evolutionary conserved ATP-independent chaperones. These proteins share a common architecture defined by a signature α-crystallin domain (ACD) flanked by highly variable N- and C-terminal extensions. The ACD, which has an immunoglobulin-like fold, plays an important role in sHSP assembly. This domain mediates dimer formation of individual protomers, which then may assemble into larger oligomers. In vertebrate sHSPs, the dimer interface is formed by the symmetrical antiparallel pairing of two β-strands (β7), generating an extended β-sheet on one face of the ACD dimer. Recent structural studies of isolated ACDs from a number of vertebrate sHSPs suggest a variability in the register of the β7/β7 strand interface, which may, in part, give rise to the polydispersity often associated with the full-length proteins. To further analyze the structure of ACD dimers, we have employed a combination of X-ray crystallography and solution small-angle X-ray scattering (SAXS) to study the ACD-containing fragments of human HSPB1 (HSP27) and HSPB6 (HSP20). Unexpectedly, the obtained crystal structure of the HSPB1 fragment does not reveal the typical β7/β7 dimers but, rather, hexamers formed by an asymmetric contact between the β4 and the β7 strands from adjacent ACDs. Nevertheless, in solution, both ACDs form stable dimers via the symmetric antiparallel interaction of β7 strands. Using SAXS, we show that it is possible to discriminate between different putative registers of the β7/β7 interface, with the results indicating that, under physiological conditions, there is only a single register of the strands for both proteins.

Articles - 3q9p mentioned but not cited (2)

  1. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8. Sehgal SA, Mannan S, Ali S. Drug Des Devel Ther 10 1605-1618 (2016)
  2. Terminal Regions Confer Plasticity to the Tetrameric Assembly of Human HspB2 and HspB3. Clark AR, Vree Egberts W, Kondrat FDL, Hilton GR, Ray NJ, Cole AR, Carver JA, Benesch JLP, Keep NH, Boelens WC, Slingsby C. J. Mol. Biol. 430 3297-3310 (2018)

Reviews citing this publication (12)

  1. Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment? Choi SK, Kam H, Kim KY, Park SI, Lee YS. Cancers (Basel) 11 (2019)
  2. The role of αB-crystallin in skeletal and cardiac muscle tissues. Dimauro I, Antonioni A, Mercatelli N, Caporossi D. Cell Stress Chaperones 23 491-505 (2018)
  3. Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell. Arrigo AP. Cell Stress Chaperones 22 517-529 (2017)
  4. Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival. Piri N, Kwong JM, Gu L, Caprioli J. Prog Retin Eye Res 52 22-46 (2016)
  5. Medical implications of understanding the functions of human small heat shock proteins. Mymrikov EV, Haslbeck M. Expert Rev Proteomics 12 295-308 (2015)
  6. Small heat-shock proteins: important players in regulating cellular proteostasis. Treweek TM, Meehan S, Ecroyd H, Carver JA. Cell. Mol. Life Sci. 72 429-451 (2015)
  7. Chaperoning heat shock proteins: proteomic analysis and relevance for normal and dystrophin-deficient muscle. Brinkmeier H, Ohlendieck K. Proteomics Clin Appl 8 875-895 (2014)
  8. Contribution of small heat shock proteins to muscle development and function. Dubińska-Magiera M, Jabłońska J, Saczko J, Kulbacka J, Jagla T, Daczewska M. FEBS Lett. 588 517-530 (2014)
  9. Evolution of crystallins for a role in the vertebrate eye lens. Slingsby C, Wistow GJ, Clark AR. Protein Sci. 22 367-380 (2013)
  10. One size does not fit all: the oligomeric states of αB crystallin. Delbecq SP, Klevit RE. FEBS Lett. 587 1073-1080 (2013)
  11. Mutations of small heat shock proteins and human congenital diseases. Datskevich PN, Nefedova VV, Sudnitsyna MV, Gusev NB. Biochemistry Mosc. 77 1500-1514 (2012)
  12. Large potentials of small heat shock proteins. Mymrikov EV, Seit-Nebi AS, Gusev NB. Physiol. Rev. 91 1123-1159 (2011)

Articles citing this publication (33)

  1. Small heat shock proteins and α-crystallins: dynamic proteins with flexible functions. Basha E, O'Neill H, Vierling E. Trends Biochem. Sci. 37 106-117 (2012)
  2. The structured core domain of αB-crystallin can prevent amyloid fibrillation and associated toxicity. Hochberg GK, Ecroyd H, Liu C, Cox D, Cascio D, Sawaya MR, Collier MP, Stroud J, Carver JA, Baldwin AJ, Robinson CV, Eisenberg DS, Benesch JL, Laganowsky A. Proc. Natl. Acad. Sci. U.S.A. 111 E1562-70 (2014)
  3. Heterooligomeric complexes of human small heat shock proteins. Mymrikov EV, Seit-Nebi AS, Gusev NB. Cell Stress Chaperones 17 157-169 (2012)
  4. Binding determinants of the small heat shock protein, αB-crystallin: recognition of the 'IxI' motif. Delbecq SP, Jehle S, Klevit R. EMBO J. 31 4587-4594 (2012)
  5. Sequence, structure, and dynamic determinants of Hsp27 (HspB1) equilibrium dissociation are encoded by the N-terminal domain. McDonald ET, Bortolus M, Koteiche HA, Mchaourab HS. Biochemistry 51 1257-1268 (2012)
  6. The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan. Lin KP, Soong BW, Yang CC, Huang LW, Chang MH, Lee IH, Antonellis A, Lee YC. PLoS ONE 6 e29393 (2011)
  7. Monomeric 14-3-3ζ has a chaperone-like activity and is stabilized by phosphorylated HspB6. Sluchanko NN, Artemova NV, Sudnitsyna MV, Safenkova IV, Antson AA, Levitsky DI, Gusev NB. Biochemistry 51 6127-6138 (2012)
  8. Structural Basis for the Interaction of a Human Small Heat Shock Protein with the 14-3-3 Universal Signaling Regulator. Sluchanko NN, Beelen S, Kulikova AA, Weeks SD, Antson AA, Gusev NB, Strelkov SV. Structure 25 305-316 (2017)
  9. Crystal structure of an activated variant of small heat shock protein Hsp16.5. McHaourab HS, Lin YL, Spiller BW. Biochemistry 51 5105-5112 (2012)
  10. Dissecting the functional role of the N-terminal domain of the human small heat shock protein HSPB6. Heirbaut M, Beelen S, Strelkov SV, Weeks SD. PLoS ONE 9 e105892 (2014)
  11. Molecular structure and dynamics of the dimeric human small heat shock protein HSPB6. Weeks SD, Baranova EV, Heirbaut M, Beelen S, Shkumatov AV, Gusev NB, Strelkov SV. J. Struct. Biol. 185 342-354 (2014)
  12. A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis. Rajagopal P, Tse E, Borst AJ, Delbecq SP, Shi L, Southworth DR, Klevit RE. Elife 4 (2015)
  13. Characterization of Mutants of Human Small Heat Shock Protein HspB1 Carrying Replacements in the N-Terminal Domain and Associated with Hereditary Motor Neuron Diseases. Muranova LK, Weeks SD, Strelkov SV, Gusev NB. PLoS ONE 10 e0126248 (2015)
  14. Structure of the α-crystallin domain from the redox-sensitive chaperone, HSPB1. Rajagopal P, Liu Y, Shi L, Clouser AF, Klevit RE. J. Biomol. NMR 63 223-228 (2015)
  15. The preferential heterodimerization of human small heat shock proteins HSPB1 and HSPB6 is dictated by the N-terminal domain. Heirbaut M, Lermyte F, Martin EM, Beelen S, Verschueren T, Sobott F, Strelkov SV, Weeks SD. Arch. Biochem. Biophys. 610 41-50 (2016)
  16. A chemical proteomics approach reveals Hsp27 as a target for proapoptotic clerodane diterpenes. Faiella L, Piaz FD, Bisio A, Tosco A, De Tommasi N. Mol Biosyst 8 2637-2644 (2012)
  17. Structure and properties of G84R and L99M mutants of human small heat shock protein HspB1 correlating with motor neuropathy. Nefedova VV, Sudnitsyna MV, Strelkov SV, Gusev NB. Arch. Biochem. Biophys. 538 16-24 (2013)
  18. A S52P mutation in the 'α-crystallin domain' of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function. Nandi SK, Rehna EA, Panda AK, Shiburaj S, Dharmalingam K, Biswas A. FEBS J. 280 5994-6009 (2013)
  19. Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress. Ylikallio E, Konovalova S, Dhungana Y, Hilander T, Junna N, Partanen JV, Toppila JP, Auranen M, Tyynismaa H. BBA Clin 3 233-242 (2015)
  20. Specific sequences in the N-terminal domain of human small heat-shock protein HSPB6 dictate preferential hetero-oligomerization with the orthologue HSPB1. Heirbaut M, Lermyte F, Martin EM, Beelen S, Sobott F, Strelkov SV, Weeks SD. J. Biol. Chem. 292 9944-9957 (2017)
  21. pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1. Clouser AF, Klevit RE. Cell Stress Chaperones 22 569-575 (2017)
  22. Chaperone function of two small heat shock proteins from maize. Klein RD, Chidawanyika T, Tims HS, Meulia T, Bouchard RA, Pett VB. Plant Sci. 221-222 48-58 (2014)
  23. Identification of subunit-subunit interaction sites in αA-WT crystallin and mutant αA-G98R crystallin using isotope-labeled cross-linker and mass spectrometry. Kannan R, Santhoshkumar P, Mooney BP, Sharma KK. PLoS ONE 8 e65610 (2013)
  24. Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain. Moutaoufik MT, Morrow G, Maaroufi H, Férard C, Finet S, Tanguay RM. Cell Stress Chaperones 22 455-466 (2017)
  25. Proline isomerization in the C-terminal region of HSP27. Alderson TR, Benesch JLP, Baldwin AJ. Cell Stress Chaperones 22 639-651 (2017)
  26. Characterization of human small heat shock protein HSPB1 α-crystallin domain localized mutants associated with hereditary motor neuron diseases. Weeks SD, Muranova LK, Heirbaut M, Beelen S, Strelkov SV, Gusev NB. Sci Rep 8 688 (2018)
  27. Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary motor neuropathy 2B in Japan. Tanabe H, Higuchi Y, Yuan JH, Hashiguchi A, Yoshimura A, Ishihara S, Nozuma S, Okamoto Y, Matsuura E, Ishiura H, Mitsui J, Takashima R, Kokubun N, Maeda K, Asano Y, Sunami Y, Kono Y, Ishigaki Y, Yanamoto S, Fukae J, Kida H, Morita M, Tsuji S, Takashima H. J. Peripher. Nerv. Syst. 23 40-48 (2018)
  28. Oligomeric structure and chaperone-like activity of Drosophila melanogaster mitochondrial small heat shock protein Hsp22 and arginine mutants in the alpha-crystallin domain. Dabbaghizadeh A, Finet S, Morrow G, Moutaoufik MT, Tanguay RM. Cell Stress Chaperones 22 577-588 (2017)
  29. Concatenation of 14-3-3 with partner phosphoproteins as a tool to study their interaction. Tugaeva KV, Kalacheva DI, Cooley RB, Strelkov SV, Sluchanko NN. Sci Rep 9 15007 (2019)
  30. Effect of N-terminal region of nuclear Drosophila melanogaster small heat shock protein DmHsp27 on function and quaternary structure. Moutaoufik MT, Morrow G, Finet S, Tanguay RM. PLoS ONE 12 e0177821 (2017)
  31. Functional and structural characterization of HspB1/Hsp27 from Chinese hamster ovary cells. Sha E, Nakamura M, Ankai K, Yamamoto YY, Oka T, Yohda M. FEBS Open Bio 9 1826-1834 (2019)
  32. Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of 'quasi-ordered' states. Clouser AF, Baughman HE, Basanta B, Guttman M, Nath A, Klevit RE. Elife 8 (2019)
  33. Local unfolding of the HSP27 monomer regulates chaperone activity. Alderson TR, Roche J, Gastall HY, Dias DM, Pritišanac I, Ying J, Bax A, Benesch JLP, Baldwin AJ. Nat Commun 10 1068 (2019)