Lecture 16 March 10th 2006 CSC2427H Algorithm in Molecular Biology CSC2427H Algorithm in Molecular Biology Lecture 16 Protein Structure Overview Lecturer Michael Brudno Scribe Jifang Jiang March 10th 2006 1 Introduction DNA RNA Protein Transcription Translation Figure 1 The production of protein RNA is transcribed from DNA and then translates into protein Protein is a sequence of amino acids It is built from 20 amino acids eg MACILVGT It starts on M MET Methionine since M is translation of start codon AUG indicates the end of the sequence Stop codon does not code any amino acid 2 Distinct aspects of Protein Structures 2 1 Primary structure The sequence of amino acid is considered as primary structure Amino acids are joined together by peptide bond The peptide linkages along with the alpha carbons to which side chain are attached form the protein backbone Page 1 of 4 Lecture 16 March 10th 2006 CSC2427H Algorithm in Molecular Biology Figure 2 Protein Sequence Each type of protein differs in its sequence and number of amino acids The two ends of a polypeptide chain are chemically different the end carrying the free amino group NH3 also written NH2 is the amino or N terminus and that carrying the free carboxyl group COO also written COOH is the carboxyl or C terminus The amino acid sequence of a protein is always presented in the N to C direction reading from left to right 1 2 2 Secondary Structure As being synthesized most polypeptide chains fold up into a stable 3D structure A few characteristic patterns appear frequently in folded structure The most common substructures include alpha helices and beta sheets a b c Figure 3 Secondary Structures a Both alpha helices and beta sheets structure b alpha helix structure c beta sheet structure Copyright C 2000 2001 2002 Free Software Foundation Inc Page 2 of 4 Lecture 16 March 10th 2006 CSC2427H Algorithm in Molecular Biology An alpha helix is a 5 4 wide corkscrew type structure where the side chains project outward from the helix Each amino acid results in a 100 turn in the helix and corresponds to a translation of 1 5 along the axis The amino acids chain has 3 6 amino acids per turn in alpha helix 3 The helix is formed by hydrogen bonds between the CO group of each amino acid and the NH group of the residue four positions C terminal n 4 Some amino acids have a greater tendency to be found in alpha helix Alanine glutamine leucine and methionine are commonly found in alpha helices whereas praline glycine tyrosine and serine usually are not 2 The beta sheet consists of two or more polypeptide chain that are arranged adjacently and in parallel within the same protein but with alternating orientation such that hydrogen bound can form between the two strands The amino acid chain is almost fully extended throughout the strand The C atoms of adjacent strands stand 3 50 apart 4 The structure of protein can be experimentally determined using MR crystallography which is expensive and time consuming Around 30 000 40 000 protein structures are known so far There is a contest held every year called CASP to see who can predict the structure of protein best 2 3 Tertiary Structure It is the three dimensional folding model of a protein It describes the overall structure of various parts including each atom position in protein In the protein structure an independently folded unit is called a protein domain It is often joined by a flexible segment of the polypeptide chain The structure of protein is not rigid Many factors can cause the orientation of backbone being changed such as heat PH oxidants Many diseases are due to the protein can not fold correctly such as mad cow disease 3 Structural Classification of Protein SCOP database If two protein sequences share 25 residues then they are considered coming from the same gene sequence and their structure are almost identical The proteins with same structure will have same function Therefore structure of a protein plays an important role in predicting the function of newly discovered protein The SCOP database is largely manual classification of proteins One of SCOP mirror site http scop berkeley edu index html It organizes proteins in a hierarchy way from class down to fold superfamily and family SCOP defines 10 classes on the top level based on similarities of their structure All alpha proteins All beta proteins Alpha and beta proteins a b Mainly parallel beta sheets beta alpha beta units Alpha and beta proteins a b Mainly antiparallel beta sheets segregated alpha and beta regions Multi domain proteins alpha and beta Folds consisting of two or more domains belonging to different classes Membrane and cell surface proteins and peptides Small proteins Usually dominated by metal ligand heme and or disulfide bridges Peptides Page 3 of 4 Lecture 16 March 10th 2006 CSC2427H Algorithm in Molecular Biology Designed proteins Non protein structures Actually the last three are not true classes There are many folds in each class For example Fold Globinlike is in the first class all alpha protein It has a core of 6 helices folded leaf partly opened SCOP is a valuable resource of protein data structure In SCOP database proteins with similar sequences or similar structures and functions are considered have a solid evolutionary link and will be grouped as families and share common ancestry Therefore SCOP has detailed evolutionary information But since it is almost completely manually derived some families or folds may not be as thoroughly detailed as others protein structural databases CATH and FSSP which are a combination of manual and automated and purely automated respectively 5 Reference 1 http www accessexcellence org RC VL GG prot Struct html nd 2 Andreas D Baxevanis Bioinformatics A Practical Guide to the Analysis of Genes and Proteins 2 Edition P263 3 http en wikipedia org wiki Alpha helix 4 http en wikipedia org wiki Beta sheet 5 Caroline Hadley and David T Jones A systematic comparison of protein structure classifications SCOP CATH and FSSP Structure 7 9 1999 1099 1112 Page 4 of 4