Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Lamin Filament Assembly Derived from the Atomic Structure of the Antiparallel Four-Helix Bundle

  • Jinsook Ahn (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University) ;
  • Inseong Jo (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University) ;
  • Soyeon Jeong (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University) ;
  • Jinwook Lee (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University) ;
  • Nam-Chul Ha (Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University)
  • Received : 2022.09.15
  • Accepted : 2022.12.19
  • Published : 2023.05.31
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Abstract

The nucleoskeletal protein lamin is primarily responsible for the mechanical stability of the nucleus. The lamin assembly process requires the A11, A22, and ACN binding modes of the coiled-coil dimers. Although X-ray crystallography and chemical cross-linking analysis of lamin A/C have provided snapshots of A11 and ACN binding modes, the assembly mechanism of the entire filament remains to be explained. Here, we report a crystal structure of a coil 2 fragment, revealing the A22 interaction at the atomic resolution. The structure showed detailed structural features, indicating that two coiled-coil dimers of the coil 2 subdomain are separated and then re-organized into the antiparallel-four-helix bundle. Furthermore, our findings suggest that the ACN binding mode between coil 1a and the C-terminal part of coil 2 when the A11 tetramers are arranged by the A22 interactions. We propose a full assembly model of lamin A/C with the curvature around the linkers, reconciling the discrepancy between the in situ and in vitro observations. Our model accounts for the balanced elasticity and stiffness of the nuclear envelopes, which is essential in protecting the cellular nucleus from external pressure.

Keywords

Acknowledgement

We would like to thank the Pohang Accelerator Laboratory 5C beamline (Pohang, Republic of Korea) for the X-ray diffraction experiments and the Korea Basic Science Institute (Ochang, Republic of Korea) for the SEC-MALS analysis. This research was supported by grants from the National Research Foundation of Korea (2019R1A2C2085135 and 2020R1A4A1019322 to N.-C.H., and 2021R1I1A1A01049976 to J.A.). This work was also supported by the BK21 Plus Program of the Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.

References

  1. Afonine, P.V., Mustyakimov, M., Grosse-Kunstleve, R.W., Moriarty, N.W., Langan, P., and Adams, P.D. (2010). Joint X-ray and neutron refinement with phenix.refine. Acta Crystallogr. D Biol. Crystallogr. 66(Pt 11), 1153-1163. https://doi.org/10.1107/S0907444910026582
  2. Ahn, J., Jeong, S., Kang, S.M., Jo, I., Park, B.J., and Ha, N.C. (2020). Separation of coiled-coil structures in lamin A/C is required for the elongation of the filament. Cells 10, 55.
  3. Ahn, J., Jeong, S., Kang, S.M., Jo, I., Park, B.J., and Ha, N.C. (2022). Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation. Commun. Biol. 5, 267.
  4. Ahn, J., Jo, I., Kang, S.M., Hong, S., Kim, S., Jeong, S., Kim, Y.H., Park, B.J., and Ha, N.C. (2019). Structural basis for lamin assembly at the molecular level. Nat. Commun. 10, 3757.
  5. Ahn, J., Lee, J., Jeong, S., Kang, S.M., Park, B.J., and Ha, N.C. (2021). Beta-strand-mediated dimeric formation of the Ig-like domains of human lamin A/C and B1. Biochem. Biophys. Res. Commun. 550, 191-196. https://doi.org/10.1016/j.bbrc.2021.02.102
  6. Akdel, M., Pires, D.E.V., Porta Pardo, E., Janes, J., Zalevsky, A.O., Meszaros, B., Bryant, P., Good, L.L., Laskowski, R.A., Pozzati, G., et al. (2021). A structural biology community assessment of AlphaFold 2 applications. BioRxiv, https://doi.org/10.1101/2021.09.26.461876
  7. Arslan, M., Qin, Z., and Buehler, M.J. (2011). Coiled-coil intermediate filament stutter instability and molecular unfolding. Comput. Methods Biomech. Biomed. Engin. 14, 483-489. https://doi.org/10.1080/10255842.2011.560147
  8. Caballero, I., Sammito, M., Millan, C., Lebedev, A., Soler, N., and Uson, I. (2018). ARCIMBOLDO on coiled coils. Acta Crystallogr. D Struct. Biol. 74(Pt 3), 194-204. https://doi.org/10.1107/S2059798317017582
  9. Chernyatina, A.A., Guzenko, D., and Strelkov, S.V. (2015). Intermediate filament structure: the bottom-up approach. Curr. Opin. Cell Biol. 32, 65-72. https://doi.org/10.1016/j.ceb.2014.12.007
  10. Chernyatina, A.A., Nicolet, S., Aebi, U., Herrmann, H., and Strelkov, S.V. (2012). Atomic structure of the vimentin central alpha-helical domain and its implications for intermediate filament assembly. Proc. Natl. Acad. Sci. U. S. A. 109, 13620-13625. https://doi.org/10.1073/pnas.1206836109
  11. Coulombe, P.A. and Wong, P. (2004). Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nat. Cell Biol. 6, 699-706. https://doi.org/10.1038/ncb0804-699
  12. Deng, Y., Liu, J., Zheng, Q., Eliezer, D., Kallenbach, N.R., and Lu, M. (2006). Antiparallel four-stranded coiled coil specified by a 3-3-1 hydrophobic heptad repeat. Structure 14, 247-255. https://doi.org/10.1016/j.str.2005.10.010
  13. Dittmer, T.A. and Misteli, T. (2011). The lamin protein family. Genome Biol. 12, 222.
  14. Emsley, P. and Cowtan, K. (2004). Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60(Pt 12 Pt 1), 2126-2132. https://doi.org/10.1107/S0907444904019158
  15. Evans, R., O'Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Zidek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021). Protein complex prediction with AlphaFold-Multimer. BioRxiv, https://doi.org/10.1101/2021.10.04.463034
  16. Heo, L., Lee, H., and Seok, C. (2016). GalaxyRefineComplex: refinement of protein-protein complex model structures driven by interface repacking. Sci. Rep. 6, 32153.
  17. Heo, L., Park, S., and Seok, C. (2021). GalaxyWater-wKGB: prediction of water positions on protein structure using wKGB statistical potential. J. Chem. Inf. Model. 61, 2283-2293. https://doi.org/10.1021/acs.jcim.0c01434
  18. Herrmann, H. and Aebi, U. (2016). Intermediate filaments: structure and assembly. Cold Spring Harb. Perspect. Biol. 8, a018242.
  19. Herrmann, H., Bar, H., Kreplak, L., Strelkov, S.V., and Aebi, U. (2007). Intermediate filaments: from cell architecture to nanomechanics. Nat. Rev. Mol. Cell Biol. 8, 562-573. https://doi.org/10.1038/nrm2197
  20. Herrmann, H. and Strelkov, S.V. (2011). History and phylogeny of intermediate filaments: now in insects. BMC Biol. 9, 16.
  21. Hess, B., Kutzner, C., van der Spoel, D., and Lindahl, E. (2008). GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447. https://doi.org/10.1021/ct700301q
  22. Huang, J., Rauscher, S., Nawrocki, G., Ran, T., Feig, M., de Groot, B.L., Grubmuller, H., and MacKerell, A.D., Jr. (2017). CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat. Methods 14, 71-73. https://doi.org/10.1038/nmeth.4067
  23. Jeong, S., Ahn, J., Jo, I., Kang, S.M., Park, B.J., Cho, H.S., Kim, Y.H., and Ha, N.C. (2022). Cyclin-dependent kinase 1 depolymerizes nuclear lamin filaments by disrupting the head-to-tail interaction of the lamin central rod domain. J. Biol. Chem. 298, 102256.
  24. Jo, S., Kim, T., Iyer, V.G., and Im, W. (2008). CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859-1865. https://doi.org/10.1002/jcc.20945
  25. Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Zidek, A., Potapenko, A., et al. (2021). Highly accurate protein structure prediction with AlphaFold. Nature 596, 583-589. https://doi.org/10.1038/s41586-021-03819-2
  26. Karantza, V. (2011). Keratins in health and cancer: more than mere epithelial cell markers. Oncogene 30, 127-138. https://doi.org/10.1038/onc.2010.456
  27. Lee, C.H., Kim, M.S., Chung, B.M., Leahy, D.J., and Coulombe, P.A. (2012). Structural basis for heteromeric assembly and perinuclear organization of keratin filaments. Nat. Struct. Mol. Biol. 19, 707-715. https://doi.org/10.1038/nsmb.2330
  28. Lilina, A.V., Chernyatina, A.A., Guzenko, D., and Strelkov, S.V. (2020). Lateral A11 type tetramerization in lamins. J. Struct. Biol. 209, 107404.
  29. Lupas, A.N. and Bassler, J. (2017). Coiled coils - a model system for the 21st century. Trends Biochem. Sci. 42, 130-140. https://doi.org/10.1016/j.tibs.2016.10.007
  30. Lupas, A.N., Bassler, J., and Dunin-Horkawicz, S. (2017). The structure and topology of alpha-helical coiled coils. Subcell. Biochem. 82, 95-129. https://doi.org/10.1007/978-3-319-49674-0_4
  31. Makarov, A.A., Zou, J., Houston, D.R., Spanos, C., Solovyova, A.S., CardenalPeralta, C., Rappsilber, J., and Schirmer, E.C. (2019). Lamin A molecular compression and sliding as mechanisms behind nucleoskeleton elasticity. Nat. Commun. 10, 3056.
  32. Nicolet, S., Herrmann, H., Aebi, U., and Strelkov, S.V. (2010). Atomic structure of vimentin coil 2. J. Struct. Biol. 170, 369-376. https://doi.org/10.1016/j.jsb.2010.02.012
  33. Ondrej, V., Lukasova, E., Krejci, J., Matula, P., and Kozubek, S. (2008). Lamin A/C and polymeric actin in genome organization. Mol. Cells 26, 356-361. https://doi.org/10.1016/S1016-8478(23)14008-8
  34. Otwinowski, Z. and Minor, W. (1997). Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326. https://doi.org/10.1016/S0076-6879(97)76066-X
  35. Pronk, S., Pall, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., Shirts, M.R., Smith, J.C., Kasson, P.M., van der Spoel, D., et al. (2013). GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845-854. https://doi.org/10.1093/bioinformatics/btt055
  36. Qin, Z. and Buehler, M.J. (2011). Flaw tolerance of nuclear intermediate filament lamina under extreme mechanical deformation. ACS Nano 5, 3034-3042. https://doi.org/10.1021/nn200107u
  37. Sammito, M., Millan, C., Frieske, D., Rodriguez-Freire, E., Borges, R.J., and Uson, I. (2015). ARCIMBOLDO_LITE: single-workstation implementation and use. Acta Crystallogr. D Biol. Crystallogr. 71(Pt 9), 1921-1930. https://doi.org/10.1107/S1399004715010846
  38. Sapra, K.T., Qin, Z., Dubrovsky-Gaupp, A., Aebi, U., Muller, D.J., Buehler, M.J., and Medalia, O. (2020). Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina. Nat. Commun. 11, 6205.
  39. Schrodinger, LLC (2015). The PyMOL Molecular Graphics System, Version 1.8.
  40. Smith, T.A., Strelkov, S.V., Burkhard, P., Aebi, U., and Parry, D.A. (2002). Sequence comparisons of intermediate filament chains: evidence of a unique functional/structural role for coiled-coil segment 1A and linker L1. J. Struct. Biol. 137, 128-145. https://doi.org/10.1006/jsbi.2002.4438
  41. Stalmans, G., Lilina, A.V., Vermeire, P.J., Fiala, J., Novak, P., and Strelkov, S.V. (2020). Addressing the molecular mechanism of longitudinal lamin assembly using chimeric fusions. Cells 9, 1633.
  42. Steinert, P.M. (1993). Structure, function, and dynamics of keratin intermediate filaments. J. Invest. Dermatol. 100, 729-734. https://doi.org/10.1111/1523-1747.ep12475665
  43. Stiekema, M., van Zandvoort, M., Ramaekers, F.C.S., and Broers, J.L.V. (2020). Structural and mechanical aberrations of the nuclear lamina in disease. Cells 9, 1884.
  44. Strelkov, S.V. and Burkhard, P. (2002). Analysis of alpha-helical coiled coils with the program TWISTER reveals a structural mechanism for stutter compensation. J. Struct. Biol. 137, 54-64. https://doi.org/10.1006/jsbi.2002.4454
  45. Strelkov, S.V., Herrmann, H., Geisler, N., Wedig, T., Zimbelmann, R., Aebi, U., and Burkhard, P. (2002). Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly. EMBO J. 21, 1255-1266. https://doi.org/10.1093/emboj/21.6.1255
  46. Strelkov, S.V., Schumacher, J., Burkhard, P., Aebi, U., and Herrmann, H. (2004). Crystal structure of the human lamin A coil 2B dimer: implications for the head-to-tail association of nuclear lamins. J. Mol. Biol. 343, 1067-1080. https://doi.org/10.1016/j.jmb.2004.08.093
  47. Szeverenyi, I., Cassidy, A.J., Chung, C.W., Lee, B.T., Common, J.E., Ogg, S.C., Chen, H., Sim, S.Y., Goh, W.L., Ng, K.W., et al. (2008). The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases. Hum. Mutat. 29, 351-360. https://doi.org/10.1002/humu.20652
  48. Turgay, Y., Eibauer, M., Goldman, A.E., Shimi, T., Khayat, M., Ben-Harush, K., Dubrovsky-Gaupp, A., Sapra, K.T., Goldman, R.D., and Medalia, O. (2017). The molecular architecture of lamins in somatic cells. Nature 543, 261-264. https://doi.org/10.1038/nature21382
  49. Turgay, Y. and Medalia, O. (2017). The structure of lamin filaments in somatic cells as revealed by cryo-electron tomography. Nucleus 8, 475-481. https://doi.org/10.1080/19491034.2017.1337622
  50. Ungricht, R. and Kutay, U. (2017). Mechanisms and functions of nuclear envelope remodelling. Nat. Rev. Mol. Cell Biol. 18, 229-245. https://doi.org/10.1038/nrm.2016.153
  51. Vermeire, P.J., Stalmans, G., Lilina, A.V., Fiala, J., Novak, P., Herrmann, H., and Strelkov, S.V. (2021). Molecular interactions driving intermediate filament assembly. Cells 10, 2457.