1. Classification: understanding the diversity and principles of
protein structure and function
MCSG 2001 structures

2. Protein structure classification
Main reference: Robert B. Russell (2002) Classification of Protein Folds. Molecular Biotechnology 20:17-28.
Importance: central to studies of protein structure, function, and evolution
Philosophy: phyletic vs. phenetic
Method: structure comparison + human knowledge

3. Approaches Hierarchical
Based on the types and arrangements of secondary structures
Unit (level): domain
Domain assignment
- structural vs. functional (fold or function in isolation)
- automated assignment methods (structure vs. sequence)

5. Assignment of Class
All a or All b (could be subjective)
a / b (bab unit) or a + b
Other classes

6. Subjective class assignment

7. Assignment of Fold
Defined by the number, type, and arrangement of SSEs
Connectivity (e.g. circular permutation, scrambled proteins)

8. Circular Permutation (CP)B N A C B A C N C D C D
..A..B..C..D..
..C..D..A..B..

9. Circular permutation example
1nls (Concanavalin)
1led (Lectin) C N N C

10. Scrambled protein pairs
1au1a_ (Interferon-b)
2occc_ (Cytochrome C oxidase)

11. Assignment of Superfamily
Homologous even in the absence of significant sequence similarity
- certain level of structural similarity
- unusual structural features
- low but significant sequence similarity from structural alignment
- key active site residues
- sequence similarity bridges
Divergence vs. convergence

12. Assignment of Family
significant sequence similarity

13. superfolds, superfamilies, supersites
TIM barrel, Rossmann-like, ferredoxin-like, b-propellers, 4-helix bundle, Ig-like, b-jelly rolls, Oligonucleotide/oligosaccharride binding (OB) fold, SH3-like.
Structure -> function (only 50% correct)

14. Structure implicates function?

15. Classification databases
SCOP
- careful assignment of evolutionary relationships; homologous vs. analogous
CATH
- A:architecture
FSSP
- a list of structural neighbors
VAST
- NCBI’s Entrez

18. CATH

19. Common Folds

20. Unique Folds

21. Structure Comparison Evolutionary relationship
Growth factor
Cytokine
Evolutionary relationship
Structure classification

22. 9% sequence identity
Shapiro & Harris, 2000

24. Structure Comparison Tools
DALI ( )
CE ( )
VAST ( )
Prosup ( )
FLASH (