3DSIG 2014 Poster: Systematic detection of internal symmetry in proteins

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These slides are from 3DSIG 2014, presented on July 11. I describe our investigation of internal symmetry in protein structures. This is quite common (24% of domains), and has many implications for function, folding, and evolution. I introduce the CE-Symm method, described in Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P. E., & Prli, A. (2014). Systematic Detection of Internal Symmetry in Proteins Using CE-Symm. Journal of Molecular Biology, 426(11), 22552268. doi:10.1016/j.jmb.2014.03.010 I discuss the results from running CE-Symm across the PDB, as well as some particularly compelling examples. See also my poster by the same title for more details.

Transcript

  • Spencer Bliven July 11, 2014 3DSIG 2014 Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P. E., & Prli, A. (2014). Systematic Detection of Internal Symmetry in Proteins Using CE- Symm. Journal of Molecular Biology, 426(11), 22552268. PMID 24681267
  • Hemoglobin [4HHB] C2 GTP Cyclohydrolase I [1A8R] D5 Rhinovirus 2 [3DPR] Icosahedral AmtB Ammonia Channel [1U7G] C3
  • Ferredoxin-like [d2j5aa1] C2 Beta-Propeller [d1u6dx_] C6 Beta-trefoil [3JUT] C3 TIM barrel [1TIM] C8 Key: Crystallographic/NCS axis Pseudosymmetry axis
  • ! Function ! Allosteric regulation/cooperativity ! Bind ligands symmetrically (e.g. metals, palindromic DNA, channels) TATA Binding Protein [1TGH] Monod, J., Wyman, J., & Changeux, J.-P. (1965). J Mol Biol, 12, 88118.
  • ! Function ! Allosteric regulation/cooperativity ! Bind ligands symmetrically (e.g. metals, palindromic DNA, channels) ! Folding ! Prevent infinite assembly ! Subunits fold quasi- independently TATA Binding Protein [1TGH] Monod, J., Wyman, J., & Changeux, J.-P. (1965). J Mol Biol, 12, 88118. Wolynes, P. G. (1996). PNAS, 93(25), 1424914255. Crystal of Squalene synthase [3WCG]
  • ! Evolution ! Identify duplications & fusions ! Many examples of homologous quaternary symmetric/ internally symmetric proteins ! Tradeoff between monomer & oligomer Lee and Blaber. PNAS (2011) vol. 108 (1) pp. 126-30
  • E. Coli DNA polymerase III beta subunit [1mmi] ! 2 chains (C2 crystal axis) Human proliferating cell nuclear antigen [1VYM] ! 3 chains (C3 crystal axis)
  • E. Coli DNA polymerase III beta subunit [1mmi] ! 2 chains ! 6 domains (pseudo C6) Human proliferating cell nuclear antigen [1VYM] ! 3 chains ! 6 domains (pseudo C6)
  • ! 2-3 chains ! 6 domains ! 12 structural repeats (pseudo D6) Ancient 12-mer? Ancient 6-mer Bacterial DimerEukaryotic/Archaeal/ Viral Trimer Kelman, Z., & O'Donnell, M. (1995). Nucleic Acids Research, 23(18), 36133620. Neuwald, A. F., & Poleksic, A. (2000). Nucleic Acids Research, 28(18), 35703580.
  • ! Extends Combinatorial Extension (CE) algorithm for structural alignment ! Web server: source.rcsb.org/ jfatcatserver/symmetry.jsp ! Download & Source code: github.com/rcsb/symmetry (LGPL) Shindyalov, I. N., & Bourne, P. E. (1998). Protein Engineering, 11(9), 739747. Jia, Y., Dewey, T. G., Shindyalov, I. N., & Bourne, P. E. (2004). J Comput Biol, 11(5), 787799.
  • Fibroblast Growth Factor [3JUT] 120 120 Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P. E., & Prli, A. (2014). Journal of Molecular Biology, 426(11), 22552268.
  • Fibroblast Growth Factor [3JUT] 120 120 Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P. E., & Prli, A. (2014). Journal of Molecular Biology, 426(11), 22552268.
  • ! 1007 structures from SCOP superfamilies ! Manually curated ! Excludes small proteins (