BCH Graduate Survey of Biochemistry

Transcription

1 BCH 5045 Graduate Survey of Biochemistry Instructor: Charles Guy Producer: Ron Thomas Director: Glen Graham Lecture 10 Slide sets available at:

2 David L. Nelson and Michael M. Cox LEHNINGER PRINCIPLES OF BIOCHEMISTRY Fifth Edition CHAPTER 4 The Three-dimensional Structure of Proteins 2008 W. H. Freeman and Company

3 Ramachandran plots show the range of φ and ψ bond angles in proteins. A survey of many proteins whose 3-dimensional structures are known, shows that the φ and ψ bond angles fall into discrete regions of the bond angle universe. This should not be surprising as different structural forms depend on the arrangement of atoms around the peptide bonds. Then it follows that the different amino acids will favor or disfavor certain types of structures.

4 Hair is composed of alpha Keratin a right-handed alpha helix. See how the organization of the chains, protofilament and protofibril contribute to the structure of the hair shaft. Although it may not seem like it, but this arrangement of keratin chains is designed for strength. Note that the protofilaments overlap in the protofibril. In building construction, we employ the same principles to create strength and stability. The organization of the hair shaft is an example of the quaternary structural organization of proteins.

5 Spider silk is made of unique proteins-spidroins that have antiparallel beta sheet structure. Spidroins have a tripartite composition: an N-terminal non-repetitive domain, a highly repetitive central part composed of approximately 100 polyalanine/glycine rich co-segments and a C-terminal non-repetitive domain. The smaller size of glycine and alanine allow tight packing of the beta sheets and optimization of van der Waals interactions. The terminal domains are thought to have different functions. Spidroins are water soluble until fibre formation is triggered. The extended nature of the polypeptide chains in the beta sheet structure does not allow for silk to stretch, but does allow for flexibility of the material. The strands of the silk fibroin are shown emerging from the spinnerets.

6 Biochemistry in the hair salon, who knew? Reducing agents include bisulfites, thioglycolate and cysteine, and the oxidizing agent can be hydrogen peroxide

7 PDB ID: 2V53 Structure of collagen in a single chain (a) and (b), and of the triple stranded form (c) of the left-handed helical structure and also a depiction of the collagen fibrils. Again notice how the collagen triple helix coiled coil structures are staggered in the fibril. A GVMGFO motif in fibrillar collagens (O denotes 4-hydroxyproline) binds the extracellular matrix protein SPARC/osteonectin/BM-40, side view and end view of the coiled coil. Protein interactions with the collagen triple helix play a critical role in collagen fibril formation, cell adhesion, and signaling.

8 So it can be readily seen that the amino acids in a primary structure are less compact than those in an alpha helix, which is more compact than the beta conformation, and that upon folding, the linear chain of amino acids become highly compact in a globular protein. Sizes are not to scale. Oxygen-binding protein with heme group shown.

9 Oxygenbinding protein with heme group shown

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13 The interaction of the heme group with the side chains of the amino acids changes upon binding and release of the ligand. On the right, the α-carbon backbone traces illustrate how their relative positions change. Subtle changes as shown on the righthand side can be revealed by 2-dimensional NMR of the protein.

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20 Structure of deoxyhemoglobin as depicted by a ribbon diagram and a surface contour diagram. Hemoglobin has two alpha and two beta subunits and the quaternary structure and conformational shifts are important in the binding and release of oxygen and carbon dioxide. Note the placement of the four heme groups.

21 Virions, and protein coats

22 Proteins in order to carry out their intended functions must conform to a stable structure, often a 3- dimensional structure. Here are two ways to disrupt the normal protein structure, by raising and in some cases lowering the temperature, and by adding an agent (guanidine hydrochloride) that disrupts the weak bonds and interactions necessary for the functional structure.