1. Protein structure Classification Ole Lund, Associate professor, CBS, DTU.

2. OL Why classify proteins Number of solved structures grow rapidly Generate overview of structure types Detect similarities (evolutionary relationships) Set up prediction benchmarks

3. OL Classification schemes SCOP – Manual classification (A Murzin) CATH – Semi manual classification (C orengo) FSSP – Automatic classification (L Holm)

4. OL Levels in SCOP 1. Class10 2. Folds648 3. Superfamilies1007 4. Families1699 Murzin et al., 1995 http://scop.mrc-lmb.cam.ac.uk/scop/

5. OL Major classes in scop Classes – All alpha proteins – Alpha and beta proteins (a/b) – Alpha and beta proteins (a+b) – Multi-domain proteins – Membrane and cell surface proteins – Small proteins

6. OL All alpha: Hemoglobin (1bab)

7. OL All beta: Immunoglobulin (8fab)

8. OL Alpha/beta: Triosephosphate isomerase (1hti)

9. OL Alpha+beta: Lysozyme (1jsf)

10. OL Folds* Each Class may be divided into one or more folds Proteins which have the same (>~50%) secondary structure elements arranged the in the same order in the protein chain and in three dimensions are classified as having the same fold *confusingly also called fold classes

11. OL Superfamilies Superfamilies are a subdivisions of folds A superfamily contains proteins which are thought to be evolutionarily related due to – Sequence – Function – Special structural features Relationships between members of a superfamily may not be readily recognizable from the sequence alone

12. OL Families Subdivision of supefamilies Contains members whose relationship is readily recognizable from the sequence (>~25% sequence identity) Families are further subdivided in to Proteins Proteins are divided into Species – The same protein may be found in several species

13. OL Families

14. OL CATH Levels Class Architecture – This level is unique to CATH (~30 is defined) Topology – ~Fold(/superfamily) in SCOP Homologous Superfamily – ~Superfamily(/family) in SCOP http://www.biochem.ucl.ac.uk/bsm/cath_new/index.html

15. OL Architecture Same overall arrangement of secondary structures – Example: The architecture :Two layer beta sheet proteins contains different folds each with a distinct number and connectivity of strands

16. OL FSSP Fully automated classification Automatic update Database contains structural alignments Tree of protein structures

17. OL FSSP classification (MHC molecules)

18. OL Links PDB – www.rcsb.org/pdb/ www.rcsb.org/pdb/ SCOP – scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.html scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.html CATH – www.biochem.ucl.ac.uk/bsm/cath_new/index.html www.biochem.ucl.ac.uk/bsm/cath_new/index.html FSSP – http://www.bioinfo.biocenter.helsinki.fi:8080/dali/index.html http://www.bioinfo.biocenter.helsinki.fi:8080/dali/index.html