PROTEIN STRUCTURE (Donaldson, March 10,2003) What are we trying to learn about genes and their proteins: Predict function for unknown protein by comparison to known proteins. Determine the relationship of proteins to each other - evolutionary history. Alignment of amino acid sequences suggests common functions. Three dimensional structure of an unknown protein may give clues to function. Compare with 3D structures of known proteins.

Evolutionary tree showing how the globin protein family arose, starting from the most primitive oxygen- binding proteins, leghemoglobins, in plants. Molecular Cell Biology. 4th ed. Lodish, : W H Freeman & Co; c2000.

Figure 5.23 The quaternary structure of proteins

Evolutionary of  like  globin chains that carry oxygen in the blood of animals. A relatively recent gene duplication of the  -chain gene produced  G and  A, which are fetal  -like chains of identical function. The location of the globin genes in the human genome is shown at the top. Molecular Biology of the Cell. 3rd ed. Alberts, Garland Publishing; c1994

A comparison of the structure of one-chain and four-chain globins. The four-chain globin shown is hemoglobin, which is a complex of two  - and two  - globin chains. The one-chain globin in some primitive vertebrates forms a dimer that dissociates when it binds oxygen, representing an intermediate in the evolution of the four-chain globin. Molecular Biology of the Cell. 3rd ed. Alberts, Garland Publishing; c1994

Protein Structures The features and forces of proteins structure Primary sequence of amino acids Secondary interactions form coils and sheets Tertiary interactions cause coils and sheets to fold upon each other. Quaternary interactions between separate protein molecules result in multi-subunit structures. Techniques used to determine protein structure. Hemoglobin will be the main example

What are the forces between amino acid residues in a protein? Ionic interactions between oppositely charged residues can pull them together. Hydrogen Bonds - Hydrogens are partially positively charged, are attracted to partially negative oxygens. (weaker) van Der Waals - hydrophobic residues become attractive to each other when forced together by exclusion from the aqueous surroundings. (weakest)

Figure 5.22 Examples of interactions contributing to the tertiary structure of a protein

Figure 5.24 Review: the four levels of protein structure

Figure 5.26 A chaperonin in action

Protein structures are determined by two techniques X-ray diffraction of pure protein crystal Nuclear Magnetic Resonance of smaller protein molecule Usually in solution

Figure 5.27 X-ray crystallography

Figure 6.14 The induced fit between an enzyme and its substrate