Dissecting subunit interfaces in homodimeric proteins

Abstract

The subunit interfaces of 122 homodimers of known three-dimensional structure are analyzed and dissected into sets of surface patches by clustering atoms at the interface; 70 interfaces are single-patch, the others have up to six patches, often contributed by different structural domains. The average interface buries 1,940 A2 of the surface of each monomer, contains one or two patches burying 600-1,600 A2, is 65% nonpolar and includes 18 hydrogen bonds. However, the range of size and of hydrophobicity is wide among the 122 interfaces. Each interface has a core made of residues with atoms buried in the dimer, surrounded by a rim of residues with atoms that remain accessible to solvent. The core, which constitutes 77% of the interface on average, has an amino acid composition that resembles the protein interior except for the presence of arginine residues, whereas the rim is more like the protein surface. These properties of the interfaces in homodimers, which are permanent assemblies, are compared to those of protein-protein complexes where the components associate after they have independently folded. On average, subunit interfaces in homodimers are twice larger than in complexes, and much less polar due to the large fraction belonging to the core, although the amino acid compositions of the cores are similar in the two types of interfaces.

Macromolecular recognition in the Protein Data Bank

“…All but two of the weak interfaces reported in Noreen & Thornton (2003b) are standard size (noting that the reported value is ÁASA = B/2). In the sample of Bahadur et al (2003), only 20% of the interfaces are standard size; the remainder are larger, with B up to 10 000 Å 2 .…”

“…‡ Data from Table 2 of Crowley & Carrondo (2004) excluding the covalent complex adxadr. § Data from Bahadur et al (2003). } Data from Janin & Rodier (1995).…”

“…Whereas most of the 122 homodimers selected by Bahadur et al (2003) do not dissociate appreciably, Noreen & Thornton (2003b) assembled a set of weak homodimers that are in equilibrium with monomers. In either sample, all subunit interfaces have B > 900 Å 2 .…”

“…The values research papers of f buried listed in Table 1 indicate that only about one-third of the atoms that contribute to B have zero ASA in the assembly. Defining the core of an interface as the set of residues that contain these buried atoms, Bahadur et al (2003) find that the core is larger in homodimers than in complexes, but its aminoacid composition is the same. Interface cores are enriched in aromatic and aliphatic residues and depleted in the charged residues Lys, Glu and Asp, but not Arg.…”

Indirect Evidence for Self Association of Muscle Fatty Acid Binding Protein from Locusta migratoria

“…The hydrophobic patches are not related to the sizes of the proteins and only weakly to their non-polar surface fraction [28]. Ala, Lys, and Pro provide the highest contributions to non-polar surface fraction for smaller patches [29].…”