On Symmetry and Pseudo-symmetry in proteins Ismb  lbr06 prlic
Upcoming SlideShare
Loading in...5
×
 

Like this? Share it with your network

Share

On Symmetry and Pseudo-symmetry in proteins Ismb lbr06 prlic

on

  • 2,049 views

My ISMB talk ( #lbr06) - about internal pseudo-symmetry in proteins

My ISMB talk ( #lbr06) - about internal pseudo-symmetry in proteins

Statistics

Views

Total Views
2,049
Views on SlideShare
2,042
Embed Views
7

Actions

Likes
1
Downloads
12
Comments
0

3 Embeds 7

https://si0.twimg.com 5
https://twimg0-a.akamaihd.net 1
https://twitter.com 1

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

On Symmetry and Pseudo-symmetry in proteins Ismb lbr06 prlic Presentation Transcript

  • 1. Internal pseudo- symmetry in proteins Andreas Prlić, Spencer E Bliven, Peter Rose, Philippe Youkharibache, Douglas Myers-Turnbull, Phil E BourneSunday, July 15, 12
  • 2. source: www.rcsb.orgSunday, July 15, 12
  • 3. Biol. Assemblies in PDB 1 Bio. parts of a Bio. multiple Bio. One asym unit 2hhb 1hho 1h4v • Bio. Assembly assigned by • Author • calculation (PQS, PISA* and curation) * E. Krissinel and K. Henrick, J. Mol. Biol. 2007Sunday, July 15, 12
  • 4. Biol. Assemb. & Disease SNP:rs28940893 causes Metachromatic leukodystrophy (lysosomal storage disorder) asym unit ... the exchange of leucine for proline at position 426 increases the susceptibility of arylsulfatase A to lysosomal cysteine proteinases and results in a severe reduction in the half-life of the mutant polypeptides Polten A, Fluharty AL, Fluharty CB, Kappler J, von Figura K, Gieselmann V. N Engl J Med. 1991 Jan 3;324(1):18-22. Lukatela G, Krauss N, Theis K, Selmer T, Gieselmann V, von Figura K, Saenger W. Biochemistry. 1998 Mar 17;37(11):3654-64. same structure, but can’t form octamer 1E33 P->L arylsulfatase A -1AUKSunday, July 15, 12
  • 5. Symmetry in Quaternary Structure Cn:  cyclic  groups,  n  =  1,  … Dn:  dihedral  groups,  n  =  2,  … Helical,  n  =  ∞ 2XQT:  C15 1A6D:  D4 1CGM: AU  pentamer AU:  heterodimer AU  monomer BA  15-­‐mer BA  8-­‐mer ~80% of all B.A. have symmetry T:  tetrahedral,  n  =  12 O:  octahedral,  n  =  24 I:  icosahedral,  n  =  60 1J2Y:  T 1EAB:  O 1A34:  I AU  monomer AU  monomer AU  monomer BA  12-­‐mer BA  24-­‐mer BA  60-­‐merSunday, July 15, 12
  • 6. It’s (pseudo-) symmetry all over the place Biol Assembly Intra Chain RNA peptidyltransferase center Rezacova et al Proteins 2007 Belousoff et al Biochem Soc. Transact. 2010 2OGG - trehalose repressor (TreR) effector binding domainSunday, July 15, 12
  • 7. Sunday, July 15, 12
  • 8. • How does this relate to protein function?Sunday, July 15, 12
  • 9. CE-Symm • new variation of CE that can detect intra-chain pseudyo- symmetries and structural repeats PDB ID 3DDV- Transcriptional regulator (GntR family) try it out: http://source.rcsb.orgSunday, July 15, 12
  • 10. N How does CE-Symm work N Variation of standard structure alignment algorithm Allows detection of Circular Permutations by duplication and truncation of atoms N Mask main diagonal of distance matrixSunday, July 15, 12
  • 11. Census of internal pseudo-symmetry • ~ 20% of all protein domains have intra- chain pseudo-symmetrySunday, July 15, 12
  • 12. •Symmetry around active sites 3HDP - Glyoxalase I •Function along symmetry 1KPK - Chloride channel interfacesSunday, July 15, 12
  • 13. •Duplication of active sites as a 1XKR - Chemotaxis protein results of internal duplications CheC •Multiple levels of symmetry 2AAY -EPSP synthetaseSunday, July 15, 12
  • 14. • What can we do if we know about internal pseudo-symmetry? • Take it for a database search • Look at the functionSunday, July 15, 12
  • 15. Example: 3HDP - Glyoxalase-ISunday, July 15, 12
  • 16. Glyoxalase I • Many metal binding proteins have this motif PDB ID 1F9Z- BOUND GLYOXALASE I FROM ESCHERICHIA COLI Molly Min He et. all 2000Sunday, July 15, 12
  • 17. A distant Glyoxalase I relative... GTP binding regulator jFATCAT structure alignment of 1VR8.A and 3HDP.A alignment requires 1 twist. There is a central topology-swapped strand.Sunday, July 15, 12
  • 18. •Protein with novel fold. •Can use symmetry 2F9H - PTSIIA/GutA-like to infer conserved •sequence motif 21% ID in CE-symm alignmentSunday, July 15, 12
  • 19. 2F9H - PTSIIA/GutA-like 21% ID in structure alignmentSunday, July 15, 12
  • 20. green ... blue ... symmetric motif Would be nice to take it into the lab and look at the function a bit more...Sunday, July 15, 12
  • 21. Hypothesis • Hypothesis: pseudo-symmetries are often related to function • Knowledge of pseudo-symmetry also gives clues about evolutionary processesSunday, July 15, 12
  • 22. Implications for Classification • Our current approaches for protein structure classification can’t describe remote relationships on sub-domain levelSunday, July 15, 12
  • 23. Conclusion • 80% of all proteins that can form Bio. Assemblies have symmetry • 20% of all domains have intra-chain pseudo symmetry • Can be linked to function • => Valuable to look at intra-chain symmetries for new proteins try out CE-Sym : http://source.rcsb.orgSunday, July 15, 12
  • 24. Acknowledgments • Spencer E Bliven, • Peter Rose, • Philippe Youkharibache, • Douglas Myers-Turnbull, • Phil E BourneSunday, July 15, 12
  • 25. Bonus slideMany propellers have high sequence similarity in their bladesSunday, July 15, 12