6. Helical wheel Residues i, i+4, i+7 occur on one face of helices, and hence show definite pattern of hydrophobicity/ hydrophilicity
7. Introduction to Molecular Biophysics Association of helices: coiled coils These coiled coils have a heptad repeat abcdefg with nonpolar residues at position a and d and an electrostatic interaction between residues e and g . Isolated alpha helices are unstable in solution but are very stable in coiled coil structures because of the interactions between them The chains in a coiled-coil have the polypeptide chains aligned parallel and in exact axial register . This maximizes coil formation between chains. The coiled coil is a protein motif that is often used to control oligomerization. They involve a number of alpha-helices wound around each other in a highly organised manner, similar to the strands of a rope.
8. Introduction to Molecular Biophysics The Leucine Zipper Coiled Coil Initially identified as a structural motif in proteins involved in eukaryotic transcription. (Landschultz et al., Science 240: 1759-1763 (1988). Originally identified in the liver transcription factor C/EBP which has a Leu at every seventh position in a 28 residue segment.
9. Association of helices: coiled coils The helices do not have to run in the same direction for this type of interaction to occur, although parallel conformation is more common. Antiparallel conformation is very rare in trimers and unknown in pentamers, but more common in intramolecular dimers, where the two helices are often connected by a short loop. Chan et al., Cell 89, Pages 263-273.
17. The dihedral angles at C atom of every residue provide polypeptides requisite conformational diversity, whereby the polypeptide chain can fold into a globular shape
Stop to ask questions: leave a moment for silence. Take Home Message: define secondary structure Next part of the talk will deal with what computational tools we can use for secondary structure prediction in proteins
Take Home Message: Alpha Helix commonly observed secondary structure in proteins –looks like a corkscrew
Take Home Message – Beta sheet is a secondary structural element that is often observed in proteins, description of beta sheet structure – antiparallel strands, hydrogen bonding across strands
Take Home Message: Phi & Psi determine secondary structure In order to compute secondary structure elements in proteins, you need to understand the spacial constraints that protein sequences are under due to the rotation around peptide bond.
Take Home Message: Ramachradan was a really smart interesting scientist 1922 – 2001 Defined - A graphical representation in which the dihedral angle of rotation about the alpha-carbon to carbonyl-carbon bond in polypeptides is plotted against the dihedral angle of rotation about the alpha-carbon to nitrogen bond. Ramachandran – calculations that elegantly accounted for the structure and amino acid composition of collagen in 1954, training in physics and electrical engineering – really significant contribution early on to the field of structural biology – developed the above Rhamachandran plot in response to stereochemical critisicisms of the collagen structure – notable critic Crick. G N Ramachandran used computer models of small polypeptides to systematically vary phi and psi with the objective of finding stable conformations. For each conformation, the structure was examined for close contacts between atoms. Atoms were treated as hard spheres with dimensions corresponding to their van der Waals radii. Therefore, phi and psi angles which cause spheres to collide correspond to sterically disallowed conformations of the polypeptide backbone. In the diagram above the white areas correspond to conformations where atoms in the polypeptide come closer than the sum of their van der Waals radi. These regions are sterically disallowed for all amino acids except glycine which is unique in that it lacks a side chain. The red regions correspond to conformations where there are no steric clashes, ie these are the allowed regions namely the alpha-helical and beta-sheet conformations. The yellow areas show the allowed regions if slightly shorter van der Waals radi are used in the calculation, ie the atoms are allowed to come a little closer together. This brings out an additional region which corresponds to the left-handed alpha-helix. Today, for beginners in biochemistry protein structures are introduced with a discussion of the Ramachandran map, which also forms the cornerstone for many discussions of protein folding.
40 There are a number of advantages in forming oligomers: size without loss of stability modular construction – one gene – big protein complex catalytic sites in enzymes regulation – will return to this briefly later
