6. 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
5
3OL0 3O49
7. E. Coli DNA polymerase III beta subunit
2 chains (C2 crystal axis)
Human proliferating cell nuclear
antigen
3 chains (C3 crystal axis)
1MMI
1VYM
6
8. E. Coli DNA polymerase III beta subunit
2 chains
6 domains (pseudo C6)
Human proliferating cell nuclear
antigen
3 chains
6 domains (pseudo C6)
1MMI
1VYM
7
9. 2-3 chains
6 domains
12 structural repeats (pseudo D6)
Ancient 12-mer?
Ancient 6-mer
Eukaryotic/Archaeal/V Bacterial Dimer
iral Trimer
Kelman, Z., & O'Donnell, M. (1995). Nucleic Acids Research, 23(18), 3613–3620.
Neuwald, A. F., & Poleksic, A. (2000). Nucleic Acids Research, 28(18), 3570–3580.
8
10. Glyoxalase 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)
9
11. 10
Glyoxalase 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)
13. Extends Combinatorial Extension
(CE) algorithm for structural
alignment
Web server:
source.rcsb.org/jfatcatserver/sym
metry.jsp
Download & Source code:
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.
12
14. PTS sorbitol transporter subunit IIA
Novel fold
Solved by the Protein Structure Initiative
Structural alignment reveals a conserved sequence motif
between halves
2F9H
13
15. 24% of domains have internal symmetry
Symmetry gives clues about duplication events
Symmetry is deeply tied to protein function
CE-Symm can accurately detect internal symmetry
SCOP:d1su3a2 d1pt2a_ d1c5ka1 d1k3ia3 d1h9ya2
14
16. Paul Scherrer Institute
Guido Capitani
Kumaran Baskaran
Jose Duarte
Joseph Somody
UC San Diego/RCSB
Douglas Myers-Turnbull
Andreas Prlić
Peter Rose
Zaid Aziz
RCSB & Bourne Lab members
NIH
Philip Bourne
Philippe Youkharibache
David Landsman
Resources:
source.rcsb.org/jfatcatserver/sym
metry.jsp
github.com/rcsb/symmetry
www.slideshare.net/sbliven
Funding: NSF, NIH, DOE, Open
Science Grid
15
20. 120° 120°
Fibroblast Growth
Factor [3JUT]
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.
19
21. 120° 120°
Fibroblast Growth
Factor [3JUT]
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.
20
23. All domains from SCOPe 2.03
Interactive results:
source.rcsb.org/jfatcatserver/scopResults.jsp
Underestimate based on conservative thresholds
SCOP Class Superfamilies % Symmetric
α 507 18.5%
β 354 24.6%
α/β 244 16.8%
α+β 551 14.3%
Multi-domain 66 4.5%
Membrane 109 23.8%
Overall 1831 18.0%
22
24. 23
BtuF [1N4A]
BtuF
BtuC
BtuD
Vitamin B12 transporter BtuCD–F from E. coli [4FI3]
25. This work is licensed under a
Creative Commons Attribution-ShareAlike 3.0 Unported License.
24
Hinweis der Redaktion
Only consider symmetry present in the biological assembly
Hemoglobin chains are 44% id (60% sim)
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
Bacterial DNA Clamps are dimeric; archaic, eurkaryotic, and viral are trimeric
Processivity Fold
Bacterial DNA Clamps are dimeric; archaic, eurkaryotic, and viral are trimeric
Processivity Fold
Bacterial DNA Clamps are dimeric; archaic, eurkaryotic, and viral are trimeric
Processivity Fold
Both glyoxalase in same superfamily (d.32.1, glyoxalase), different families
GTP 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), 1661–1670. doi:10.1002/pro.5560070801
Both glyoxalase in same superfamily (d.32.1, glyoxalase), different families
GTP 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), 1661–1670. doi:10.1002/pro.5560070801
Deposited 2005
Note that Multi-domain proteins were excluded from the table. 4.5% of the 66 multi-domain superfamilies are symmetric.