Systematic detection of internal symmetry in proteins - Rheinknie Regiomeeting 2014

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Following the Evolution of New Protein Folds Via Protodomains

Spencer BlivenSeptember 24-26, 201428th Rhine-Knee Regional Meeting on BiocrystallographySystematic detection of internal symmetry in proteins

Quaternary Structure Symmetry

Hemoglobin[PDB:4HHB]C2GTP Cyclohydrolase I [1A8R]D5Rhinovirus 2[3DPR]IcosahedralAmtB Ammonia Channel[1U7G]C3

1Only consider symmetry present in the biological assemblyHemoglobin chains are 44% id (60% sim)1Internal Symmetry

Ferredoxin-like[SCOP:d2j5aa1]C2Beta-Propeller[SCOP:d1u6dx_]C6

Beta-trefoil[3JUT]C3

TIM barrel[1TIM]C8Key:Crystallographic/NCS axisPseudosymmetry axis2FunctionAllosteric regulation/cooperativityBind ligands symmetrically (e.g. metals, palindromic DNA, channels)SignificanceMonod, J., Wyman, J., & Changeux, J.-P. (1965). J Mol Biol, 12, 88118.3TATA Binding Protein [1TGH]

Hemoglobin[4HHB]63% of symmetric domains have the ligand within 5 of the axis of symmetry, 37% within 1

3FunctionAllosteric regulation/cooperativityBind ligands symmetrically (e.g. metals, palindromic DNA, channels)FoldingPrevent infinite assemblySubunits fold quasi-independentlySignificanceTATA Binding Protein [1TGH]

Monod, J., Wyman, J., & Changeux, J.-P. (1965). J Mol Biol, 12, 88118.Wolynes, P. G. (1996). PNAS, 93(25), 1424914255.4

Hemoglobin[4HHB]63% of symmetric domains have the ligand within 5 of the axis of symmetry, 37% within 1

4EvolutionIdentify duplications & fusionsMany examples of homologous quaternary symmetric/internally symmetric proteinsTradeoff between monomer & oligomerSignificanceLee and Blaber. PNAS (2011) vol. 108 (1) pp. 126-30

53OL03O4963% of symmetric domains have the ligand within 5 of the axis of symmetry, 37% within 1

5Hierarchical SymmetryDNA ClampsE. Coli DNA polymerase III beta subunit2 chains (C2 crystal axis)

Human proliferating cell nuclear antigen3 chains (C3 crystal axis)

61MMI1VYMBacterial DNA Clamps are dimeric; archaic, eurkaryotic, and viral are trimericProcessivity Fold6

Hierarchical SymmetryDNA ClampsE. Coli DNA polymerase III beta subunit2 chains6 domains (pseudo C6)

Human proliferating cell nuclear antigen3 chains6 domains (pseudo C6)

71MMI1VYMBacterial DNA Clamps are dimeric; archaic, eurkaryotic, and viral are trimericProcessivity Fold7Hierarchical SymmetryDNA Clamps2-3 chains6 domains12 structural repeats (pseudo D6)

Ancient 12-mer?Ancient 6-merBacterial DimerEukaryotic/Archaeal/Viral TrimerKelman, Z., & O'Donnell, M. (1995). Nucleic Acids Research, 23(18), 36133620.Neuwald, A. F., & Poleksic, A. (2000). Nucleic Acids Research, 28(18), 35703580.8Bacterial DNA Clamps are dimeric; archaic, eurkaryotic, and viral are trimericProcessivity Fold8Glyoxalase SuperfamilyGlyoxalase I from Clostridium acetobutylicum [3HDP](Nickel; Dimer)Glyoxalase I from E. coli [1F9Z](Nickel; Dimer)1,2-dihydroxy-naphthalene dioxygenase from Pseudomonas sp. strain C18 [2EHZ](Iron; Octamer)

9Both glyoxalase in same superfamily (d.32.1, glyoxalase), different familiesGTP regulator solved at JCSG. ORFan sequence, in the rare Mog1p fold (d.107.1)

See also Bergdoll, M., Eltis, L. D., Cameron, A. D., Dumas, P., & Bolin, J. T. (1998). All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly. Protein Science : a Publication of the Protein Society, 7(8), 16611670. doi:10.1002/pro.55600708019Glyoxalase Superfamily

10Glyoxalase I from Clostridium acetobutylicum [3HDP](Nickel; Dimer)Glyoxalase I from E. coli [1F9Z](Nickel; Dimer)1,2-dihydroxy-naphthalene dioxygenase from Pseudomonas sp. strain C18 [2EHZ](Iron; Octamer)Both glyoxalase in same superfamily (d.32.1, glyoxalase), different familiesGTP regulator solved at JCSG. ORFan sequence, in the rare Mog1p fold (d.107.1)

See also Bergdoll, M., Eltis, L. D., Cameron, A. D., Dumas, P., & Bolin, J. T. (1998). All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly. Protein Science : a Publication of the Protein Society, 7(8), 16611670. doi:10.1002/pro.5560070801101007 structures from SCOP superfamiliesManually curatedExcludes small proteins (