Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431


Fall 2008

Lecture Notes: 24 September

© R. Paselk 2008


3-D Structure of Proteins 4

Tertiary Structures, cont.

Secondary structural elements have become the basis of classifications systems of protein types based on four classes:

  1. All alpha
  2. All beta
  3. alpha/beta (have alternating alpha and beta structures, such as in the beta-alpha-beta motif)
  4. alpha + beta (local clusters of alpha and beta in same chain with each cluster consisting of contiguous primary structure).
Within these classes then, motifs, as seen in text Figure 4-20 above, can be added together to give more complex motifs/folds and used in further classification as seen in text Figure 4-21:
    1. All Alpha (text Figure 4-21 pt 1)
    2. All Beta (text Figure 4-21 pt 2)
    3. Alpha/Beta (text Figure 4-21 pt 3)
    4. Alpha + Beta (text Figure 4-21 pt 4)

Unlike the two classification laevels above, the next level is based on evolutionary relationships. Folds/Motifs are often more highly conserved than sequences, and so are used along with sequences to trace relatedness among molecules and thus organisms.


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 3-D 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 structure 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.

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.

Groups of motifs forming the core of the tertiary structures of domains are referred to as Folds. Over 600 folds have been discovered, with an expectation that about 1,000 exist, as we saw in our earlier discussion. (Note that 1,000 is a bunch, but well below the infinite number possible!)

Note also that protein classes often apply to domains of multidomain proteins, with no overall class applicable to the entire protein. Thus for IgG we see multiple domains of the same class (all beta) to make up an all beta protein, but many enzymes are made up of domains with entirely distinct folds and evolutionary backgrounds.

Quaternary Protein Structure

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

Folding Hierarchy Overview

diagram illustrating hierarchical nature of protein folding levels

Rationale for quaternary: There are a variety of advantages to large structures:

Quaternary structures allows the assembly of large to extremely large structures. 

Pathway Diagrams

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Lecture Notes

Last modified 24 September 2008