BISC 330L Biochemistry Spring 2015 USC Lecture 7 Wed Jan 28 2015 More Chapter 2 material Tertiary Structure Quaternary Structure Predicting character Tertiary Structure Shows conformation of the whole polypeptide Stabilized by noncovalent bonds sometime also by disulfide between Cys Can be studied by X ray crystallography NMR Proteins can be fibrous long and extended globular blobs An example of tertiary Structure Myoglobin The tertiary structure of protein is driven by hydrophobic interactions Yellow hydrophobic residues Amphipathic beta strand and alpha helix The tertiary structure of membrane proteins Frequently occurring tertiary folding modules Motifs supersecondary structure Motifs are small combinations of secondary structure Consecutive sequences of primary structure not distant Helix Loop Helix Motif Alpha helical segments separated by an intervening loop HLH domain preceded by a stretch of basic aa whose charged side chains contact DNA bHLH Proteins MyoD with bHLH motifs occur as dimers or heterodimers Domains Compact globular units that are connected by flexible regions Make up parts regions of a protein Can be large Stable can be associated with specific function s of protein CD4 Proteins have evolved by using common domains Quaternary Structure Most proteins are made up of more than one subunit Subunits are held together by patches of noncovalent bonds How the subunits come together to form the whole protein complex is called quaternary structure Two identical subunits homodimer Two different subunits heterodimer Hemoglobin another example Oxygen carrying protein of red blood cells Consists of two globin and two globin subunits for a total of four subunits Each of the four subunits has a similar tertiary structure to that of myoglobin Tetramer 2 2 Quaternary structure of hemoglobin Complex Protein Quaternary Structure Rhinovirus causing common cold Fig 2 55 4 subunits x 60 each form complete quaternary structure Sequence Conformation Sequence Conformation Function Function 1 Native protein 2 Treat with ME and urea 3 Denatured protein 4 Remove denaturing agents 5 Native protein returns Dialysis followed by oxidization Reagents that denature protein Sodium dodecyl sulfate SDS How sequence determine structure residue bias to secondary structure Context is important too Predict 3D structure from sequence Challenge and opportunity 1 Ab initio computation technology and understanding of 2 Based on known structures and computation modeling by molecular forces homology Intrinsically unstructured protein regions IUPs Exception to the rule metamorphic protein Protein folding is a highly cooperative process Proteins fold by progressive stabilization of intermediates Random search the Levinthal s paradox Protein folding disease Post translational modification and lys acetylation How GFP works End of Lecture 7