Understanding the role and evolution of internal symmetry in protein structure is a fundamental question in structural biology. We present here CE-Symm 2.0, a key tool to address that question, which is able to detect all types of protein internal symmetry and provides a robust and intuitive sequence-to-structure analysis of all repeats. Notable features compared to the previous version include an optimized multiple alignment between repeats, determination of the full point group, and identification of multiple symmetry axes. We expect CE-Symm to find ample use in evolutionary studies, functional annotation, and structural classification of proteins.
This work was presented at the 3DSIG 2016 conference in Orlando, FL, on July 8, 2016.
See also the poster form: http://www.slideshare.net/sbliven/3dsig-2016-poster-exploring-internal-symmetry-and-structural-repeats-with-cesymm
3DSIG 2016 Presentation: Exploring Internal Symmetry and Structural Repeats with CE-Symm
1. EXPLORING INTERNAL SYMMETRY AND
STRUCTURAL REPEATS WITH CE-SYMM
Spencer Bliven
July 8, 2016
3DSIG. Orlando, FL
2. LEVELS OF SYMMETRY: QUATERNARY SYMMETRY
DNA Clamps are found as
dimers in bacteria or
trimers in eukaryotes
DNA is bound in the
central channel
Proliferating Cell Nuclear Antigen [1VYM]
(DNA modeled from 1BNA)
Stoichiometry: A3
Symmetry: C3
1
10. CE-SYMM 2.0
Multiple alignment between all repeats
Open and Closed symmetry
Multiple Axes and hierarchical symmetry
Point Group detection
Monte Carlo alignment optimization
https://github.com/rcsb/symmetry (LGPL)
Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P. E., & Prlić, A. (2014).
Systematic Detection of Internal Symmetry in Proteins Using CE-Symm. Journal of Molecular Biology, 426(11),
2255–2268
Glyoxalase
[3B59]
D2
9
22. CENSUS
All domains from SCOPe 2.06
Underestimate based on conservative thresholds
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Order Number of Superfamilies % symmetric
Asymmetric 1051 75.39%
Rotational 302 21.66%
C2 237 78.48%
C3 19 6.29%
C4 12 3.97%
C5 2 0.66%
C6 8 2.65%
C7 16 5.30%
C8 8 2.65%
Dihedral 19 1.36%
D2 17 89.47%
D3 2 10.53%
Helical 7 0.50%
Translational 15 1.08%
23. SUMMARY
Nature utilizes symmetry at multiple levels
Internal symmetry can reveal evolutionary history of folds
Duplications & fusions can preserve the overall biological assembly
Internal symmetry is a multiple alignment problem
CE-Symm is able to automatically detect most types of structural
repeats
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24. ACKNOWLEDGEMENTS
Paul Scherrer Institute
Guido Capitani
Aleix Lafita
UC San Diego/RCSB
Douglas Myers-Turnbull
Andreas Prlić
Peter Rose
Jose Duarte
RCSB & Bourne Lab members
NIH
Philip Bourne
Philippe Youkharibache
David Landsman
Resources:
github.com/rcsb/symmetry
source.rcsb.org/jfatcatserver/sy
mmetry.jsp
www.slideshare.net/sbliven
Funding: NCBI/NLM/NIH
RCSB: NSF, NIH, DOE
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33. CE-SYMM: SELF-ALIGNMENT
Fibroblast Growth
Factor [3JUT]
120° 120°
Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P.
E., & Prlić, A. (2014). Journal of Molecular Biology, 426(11), 2255–2268.
32
34. CE-SYMM: SELF-ALIGNMENT
Fibroblast Growth
Factor [3JUT]
120° 120°
Myers-Turnbull, D., Bliven, S. E., Rose, P. W., Aziz, Z. K., Youkharibache, P., Bourne, P.
E., & Prlić, A. (2014). Journal of Molecular Biology, 426(11), 2255–2268.
33
35. βγ-CRYSTALLIN FAMILY
34
Aravind, P., Mishra, A., Suman, S. K., Jobby, M. K., Sankaranarayanan, R., & Sharma, Y. (2009). The betagamma-
crystallin superfamily contains a universal motif for binding calcium. Biochemistry, 48(51), 12180–12190.
M-Crystallin
[3HZ2.A]
C2
Bovine ɣB-Crystallin
[4GCR]
C2+C2
36. This work is licensed under a
Creative Commons Attribution-ShareAlike 3.0 Unported License.
35
Editor's Notes
63% of symmetric domains have the ligand within 5Å of the axis of symmetry, 37% within 1Å
63% of symmetric domains have the ligand within 5Å of the axis of symmetry, 37% within 1Å
63% of symmetric domains have the ligand within 5Å of the axis of symmetry, 37% within 1Å
Fatty acid synthesis proteins
TODO add double hotdog, read up more on functions
Photo public domain http://www.publicdomainpictures.net/view-image.php?image=121204&picture=hotdog-mustard-only
Top image actually 1q6w for simplicity
Fatty acid synthesis proteins
TODO add double hotdog, read up more on functions
Photo public domain http://www.publicdomainpictures.net/view-image.php?image=121204&picture=hotdog-mustard-only
Top image actually 1q6w for simplicity
Fatty acid synthesis proteins
Photo public domain http://www.publicdomainpictures.net/view-image.php?image=121204&picture=hotdog-mustard-only
https://pixabay.com/en/hot-dogs-frankfurters-bun-meat-1047824/
Fatty acid synthesis proteins
TODO add double hotdog, read up more on functions
Photo public domain http://www.publicdomainpictures.net/view-image.php?image=121204&picture=hotdog-mustard-only
Top image actually 1q6w for simplicity
Fatty acid synthesis proteins
TODO add double hotdog, read up more on functions
Photo public domain http://www.publicdomainpictures.net/view-image.php?image=121204&picture=hotdog-mustard-only
Top image actually 1q6w for simplicity