Lecture 11 Evolution, Function, and Classification of Proteins
•The Nature of Protein Sequences •Homology •Protein Phylogeny •Conjugated Proteins and Prosthetic Groups •The Biological Functions of Proteins
Nature of Protein Sequences • Sequences and composition reflect the function of the protein - form follows function • e.g. membrane proteins have more hydrophobic residues, fibrous proteins (particularly collagen) may have atypical sequences • The similarity of one protein sequence to another is called homology
Phylogeny of Cytochrome c • The number of amino acid differences between two cyt c sequences is proportional to the phylogenetic difference between the species from which they are derived • This observation can be used to build phylogenetic trees of proteins molecular evolution
Cytochrome c
Functionally Related Proteins Often Share a Common Origin • e.g. the oxygen transport proteins myoglobin (in muscle) and hemoglobin (in erythrocytes) • Remember hemoglobin is a2b2 • Hemoglobin a and hemoglobin b: 64 common residues • Hemoglobin a and myoglobin: 38 common residues
Conjugated Proteins - when 20 just isn’t enough • Proteins that comprise only amino acids are simple proteins • Some include additional non-amino acid chemical functionality - conjugated proteins • The non-protein component is the prosthetic group • Allows for chemical (eg redox, hydride transfer) and structural (eg molecular recognition) properties not covered by the common amino acids
Glycoproteins • • • •
Proteins containing carbohhydrate May be a little, e.g. immunoglobulin G Or a lot, e.g. procaryotic cell wall proteoglycans Often extracellular proteins
Lipoproteins • • • •
igG
Proteins containing lipids (fats) May be as little as a single fatty acid, e.g. protein kinase A Or a lot, e.g. plasma lipoproteins (75% lipid by weight) Plasma lipoproteins are primarily for lipid transport
Nucleoproteins • Proteins conjugated to nucleotides • e.g. ribosomes • Flavoproteins contain flavin nucleotides covalently bonded to the protein • In contrast NAD+/NADH proteins have the nucleotide non-covalently associated
And… • Metalloproteins • Hemoproteins • Phosphoproteins – often signalling proteins – phosphorylation at ser, thr, tyr OH groups
Biological Functions of Proteins Proteins are the agents of biological function • Enzymes - phosphoglucose isomerase, trypsin • Regulatory proteins –Hormones, eg insulin, enkephalins, endorphins, GSH –Transcription Factors, eg zinc fingers, GCN4 –Kinases and phosphatases • Transport proteins - hemoglobin, VDAC • Structural proteins - collagen, intermediate filaments • Contractile proteins - actin, myosin • Exotic proteins - antifreeze proteins, venoms