Molecular basis for protein-protein interactions

Abstract

This minireview provides an overview on the current knowledge of protein-protein interactions, common characterisation methods to characterise them, and their role in protein complex formation with some examples. A deep understanding of protein-protein interactions and their molecular interactions is important for a number of applications, including drug design. Protein-protein interactions and their discovery are thus an interesting avenue for understanding how protein complexes, which make up the majority of proteins, work.

Keywords: characterisation methods; heterooligomeric complex; homooligomeric complex; molecular interactions; protein–protein interactions.

Figure 1

Different methodologies employed to study PPIs. The protein used for illustration is the heterodimer of human NAD-dependent isocitrate dehydrogenase (Protein Database (PDB): 6KDF) [10]. Figure adapted from Carter et al. [11].

Figure 2

Mechanisms of homooligomeric complex formations. a) Domain swapping of RNase A (PDB: 1A2W) [73]. The swapped regions are shown in red. b) Leucine zipper of GCN4 (PDB: 1YSA) [74]. Interacting leucine residues are shown in red. Figure adapted from Hashimoto et al. [77].

Figure 3

Parts a) and b) represent the electron densities and B-factors of TMV, respectively. The cryo-EM structure of TMV at 1.9 Å, PDB: 6SAE, EMD-10129 [95] is represented by i, whereas the X-ray structure of TMV at 2.45 Å, PDB: 1EI7 [96] is represented by ii, part c) shows the assembly of TMV [95]. The cryo-EM structure was able to elucidate loop regions that were not previously resolved in the X-ray structure.

Figure 4

Schematic of the general assembly of charged protein containers to form binary nanoparticle superlattices. a) Surface engineering of the protein container to yield either positively (right) or negatively (left) charged containers. b) Nanoparticle synthesis. The different nanoparticles are illustrated in different colours. c) Self-assembly of the different charged protein containers to form a highly ordered three-dimensional superlattice. Figure reprinted with permission from J. Am. Chem. Soc. 2016, 138, 12731–12734 [103]. Copyright 2016 American Chemical Society.