1. The amino acids in their natural habitat

2. Topics: Hydrogen bonds Secondary Structure Alpha helix Beta strands & beta sheets Turns Loop Tertiary & Quarternary Structure Protein Domains

3. Hydrogen Bonds A hydrogen bond is a type of attractive (dipole-dipole) interaction between an electronegative atom and a hydrogen atom bonded to another electronegative atom. Hydrogen Bond Donors (D): Nitrogene.g. N-H amide in peptide bond Oxygene.g. O-H sidechain of Ser Hydrogen Bond Acceptors (A): Oxygene.g. C=O carbonyl in peptide bond Distance: H-A  2.5 Å; D-A  3.5 Å; also dependent on angle D-H … A

4. Hydrogen Bonds (2)

5. Secondary structure The amino acids form four different secondary structure elements: α-helices β-strands Turns Loops

6. Secondary structure: the  -helix hydrogen bond between backbone O (from C=O) of residue i and backbone H (from N-H) of residue i+4: O(i) – N(i+4) 3.6 residues per turn right-handed helix

7. The  -helix

8. Helix

9. Helix dipole All peptide unit planes are roughly parallel to the helix axis Each peptide bond is a small dipole The dipoles within the helix are aligned, i.e. all C=O groups point in the same direction and all N-H groups point the other way The helix becomes a net dipole with +0.5 charge units at the N-terminal and – 0.5 at the C-terminal By convention the dipole points from negative to positive

10. Helix summary Hydrophobicity distribution Hydrogen bond between O (i) and N (i+4) Helix dipole

11. Secondary structure – β -strand A β-sheet consists of at least two β-strands interact with each other Anti-parallelParallel

12.  -strands and  -sheets Backbone adopts an “extended” conformation:  -strand The  -strands are arranged side by side; adjacent  -strands can be parallel or anti-parallel Backbone hydrogen bonding between adjacent  -strands; formation of a  -sheet R-groups extend below and above the sheet, perpendicular to the plane of the H-bonds The strand is twisted

13. Residue direction in  -sheets R-groups of neighbouring residues within one  -strand point in opposite directions. R-groups of neighbouring residues on adjacent  -strands point in the same direction

14. Antiparallel  -sheet N -> C C <- N

15. Parallel  -sheet N -> C

16.  Bulge An irregularity in antiparallel  structures Hydrogen-bonding of two residues from one strand with one residue from the other in antiparallel  sheets

17. Strand summary Multiple strands form a sheet Hydrophobicity distribution alternating Parallel and anti-parallel strands & hydrogen bonding patterns Bulges are irregularities

18. Secondary structure – Turn Turns connect the secondary structure elements

19. Turns Specialized secondary structures that allow for chain reversal without violating conformational probabilities Nearly one-third of the amino acids in globular proteins are found in turns. Most turns occur at the surface of the molecule. A specific subclass is the  -turn, a region of the polypeptide of 4 amino acids (i, i+1, i+2, i+3, between two  -strands) having a hydrogen bond from O(i) to N(i+3).

20.  -Hairpin Widespread in globular proteins. One of the simplest super-secondary structures

21. Turn summary A turn sits between two ‘things’ A  -turn sits between two  -strands There are many types of  -turn Nearly all  -turns contain at least one Gly or Pro

22. Secondary structure - Loop A loop is everything that has no defined secondary structure

23. Tertiary structure The secondary structure elements interact to form the structured protein

24. Quaternary structure Some proteins can interact with each other to form dimers or multimers The individual chains are callled subunits or monomers

25. Protein domains - definitions Group of residues with high contact density, number of contacts within domains is higher than the number of contacts between domains. A stable unit of protein structure that can fold autonomously A rigid body linked to other domains by flexible linkers. A portion of the protein that can be active on its own if you remove it from the rest of the protein.

26. Protein Domains Domains can be 25 to 500 amino acids long; most are less than 200 amino acids The average protein contains 2 or 3 domains The same or similar domains are found in different proteins. “Nature is a ‘tinkerer’ and not an inventor” (Jacob, 1977). “Nature is smart but lazy” Usually, each domain plays a specific role in the function of the protein.

27. Protein Domains - an alphabet of functional modules WD40WWSH2SH3 14-3-3 ANK3 ARM BH1C1C2 CARD EHEVHFYVEPDZDeathDEDEFH PHPTBSAM From: Bioinformatics.ca

28. Domain Database InterPro InterPro - protein sequence analysis & classification InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. Interpro combines protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool

29. Summary 3D, 4D & domains Proteins are folded up in 3D Protein subunits can fold up to form a quarternary structure Sometimes monomer is not active, but quarternary structure is Protein domains “independent units” with own function& structure Average size 100-150 aa Lego blocks of nature Look in Interpro to find info about domains in your protein