Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431	Biochemistry	Fall 2001
Lecture Notes:: 19 September	© R. Paselk 2001
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3D Structure of Proteins III

Aside: Fibrous proteins: a-keratin (hair etc., a-helix based) (Figure 6.14 p 173) [overhead 7-11 V&V, 7-25 & 26]; stretched a-keratin (parallel b-pleated sheet) [overhead, Figure 7-26]; silk fibroin (silk, anti-parallel b-pleated sheet) (Figure 6.15 p 174) [overhead, 7-29 V&V], Collagen triple helix. (Figure 6.18 & 6.19 p 176-7) [overheads: 11-8&10, S; 4-10 to 12]

Domains

Large proteins (>200 aa's) usually fold up in smaller pieces of 100-200 aa's called domains. Recall that we define a Domain as an independent folding region in a protein. Often defined by clefts in 3D structure giving globular elements connected by "hinges" (single strand segments connecting the domains). Domains have the advantages of speeding up the folding process (fold domains independently, then assemble resultant folded domains - effectively processing folding of domains in parallel). Another advantage of domain stucture is that nature can take bits of DNA specifying particular domains with particular functions and assemble them in new combinations to get new activities (e.g. combine an ATP binding site and a sugar binding site to give a sugar phosphorylating protein).

Example: IgG , domains, exons and evolution. [overheads: IgG/proteins; 7.23 MvH]

• IgG made up of four independently synthesized proteins, 2 heavy chains with 4 domains each, and 2 light chains with 2 domains each.
  • Domain types: b-meander [anti-parallel b-sheet], b-barrel. (Note that Motifs and Domains often use the same nomenclature, and indeed often overlap. Can in fact have Motif = Domain = Tertiary structure!)
• Domains correspond to exons of DNA (frequently, but not always the case)
  • The domains are all apparently related through gene duplication in the remote past.
• The active site of IgG (2/IgG) is made up between two domains, one from a heavy chain and one from a light chain.
• When immune system is developing individual cells express single IgG molecules made from randomly expressed heavy and light chains.

In a similar manner we see that many enzymes have active sites created between two domains, often one domain binds one substrate while the second binds a second substrate.

Its as if these proteins were designed by taking "off-the-shelf" components, assembling them, and then over time (and generations) tuning the combination up.

Other Domain examples: (text figures, pp 185-191) [overheads]

Quaternary Protein Structure

Quaternary (4°) structures (overhead): Geometrically specific associations of protein subunits; the spatial arrangement of protein subunits.

Rationale for quaternary:

• Increasing the size of a protein allows better "fits" for catalysis and binding - many weak bonds are needed to maintain specific structures.
• Interacting subunits provide mechanisms for regulation.
• Can bring sequential active sites of metabolic pathways into close proximity.
• The process of folding slow tremendously with increasing size, thus folding individual subunits, and assembling these subunits can greatly enhance folding efficiency.
• Less waste due to errors - get about 1 error / 10³
• Allows the assembly of extremely large structures.

Pathway Diagrams

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Last modified 21 September 2001