Molecular Biology: Protein Structure and Functions - Stepanov V.M. 2005

Quaternary Protein Structure
Structural organization of subunit interfaces

Several types of intersubunit interaction Organization are known, characterized by distinct roles of Secondary Structure elements in contact formation. Above, using Alcohol dehydrogenase as an example, we examined in detail a fairly common mechanism based on the interaction between $\beta$-structural segments located at the periphery of adjacent subunits. This leads to The formation of an extended $\beta$-pleated sheet. Intersubunit contacts can also be formed through interactions between functional groups located On the surface of $\beta$-pleated sheets.

Other modes of quaternary structure formation are also widespread. For instance, in cytoplasmic malate dehydrogenase, the dimer is held together predominantly by noncovalent interactions within a bundle of six parallel $\alpha$-helices—three from each subunit. Naturally, the primary role here belongs to the side chains of amino acid residues positioned accordingly within the $\alpha$-helices. In The quaternary structure of certain Proteins, such as Triosephosphate isomerase, the principal role is played by peptide loops involved in establishing noncovalent contacts between subunits.

Particularly characteristic are proteins featuring specialized structures that allow for the reversible formation or Cleavage of intersubunit contacts, known as leucine zippers. Such proteins (which include an entire family of METABOLISM/31.html">Transcription regulators) possess a characteristic sequence in which every seventh position is occupied by a hydrophobic amino acid residue, most commonly leucine. When this sequence forms an $\alpha$-helix, the branched hydrophobic groups of the leucine residues form a distinctive "sparse" ridge, separated by two turns of the $\alpha$-helix (recall that its periodicity is 3.6 residues). Two such helices belonging to different subunits and oriented in the same direction coil into a double coiled-coil (cf. Section 14.3). The latter is stabilized by hydrophobic contacts between the leucine residues aligning into a dense ridge. This process is indeed reminiscent of zipping a zipper.