Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 438 - Introductory Biochemistry - Spring 2013

Lecture Notes:


3-D Structure of Proteins 3

Quaternary Protein Structure

Quaternary (4°) structures : Geometrically specific associations of protein subunits; the spatial arrangement of protein subunits. [Examples, Figure 4.26]: a = alpha2{2 identical protomers with alpha/beta barrel fold}; b = alpha2{2 identical protomers, all beta fold}; c = alpha4{4 identical protomers, all alpha, three helices/subunit; 8 helix membrane spanning bundle}; d = alpha3{3 identical protomers, beta sheets}; e = alpha2beta2; f = alpha2betagamma.

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

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

Note the occurance of oligomeric proteins of E. coli in the SWISSPROT database[Table 4.1]

Some of the large complexes are shown in Figure 4.27 for a bacterium with a very minimal genome (codes for only 689 proteins vs. about 5,000 for E. coli).

Note interactome diagram [Figure 4.30]—strengths of interactions are NOT indicated.

IgG—Domains, Folds, Multimers, Exons & Evolution

Folding Hierarchy Overview

Let's look at how the various levels of structure go ingto making a typical multimeric protein:

diagram of protein folding hierarchy

 FYI - Review/Enhancement: X-ray Diffraction determination of protein structure.

  • Review x-ray diffraction learned in Chem 109
  • Note the each crystal point now becomes many points, each with its own "reflecting" plane.
  • Rotation to determine relative locations in three space results in thousands of reflections
  • Need to add heavy metals to act as "beacons" to locate positions in absolute space, and need to do a couple of times isomorphically (without altering the proteins structure - isomorphic replacements).

Finally use Fourier transforms to convert angles and intensities of reflections to 3-D map of protein.

Aside: The reality of X-ray diffraction structures. Trouble is that most of our detailed knowledge of protein 3-D structure is due to X-ray diffraction. Problem: Non-solution, look at very concentrated, crystal structures for proteins.

Why do we think they represent reality?

  • - Crystals very hydrated, in fact some enzymes maintain activities in crystal form!
  • - Chemical exchange studies, such as deuterium exchange are consistent with residue exposure.
  • - Chemical reactivity of residues are consistent with residue exposure.
  • - Optical probes of overall shape (e.g. light and x-ray scattering) are consistent.
  • - Hydrodynamic studies of size and shape (e.g. sedimentation, gel filtration) are consistent.
  • - Optical probes of regularity/helicity (e.g. Circular dichroism and ORD) are consistent.
  • - Probes of local environment (e.g. NMR, CD & ORD, Fluorescence, UV) are consistent.
  • Note that any "non-rigid" region of the protein will not show up on X-ray diffraction image, or will be "fuzzy."
Thus quite confident of structures.



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© R. A. Paselk 2010;

Last modified 13 February 2013