Figure 1. Domain architecture determines super-molecular structure in dense phases.

(Top row) Insight into dense phase structures via high-resolution structures of domain/motif interactions. (Left) A high resolution crystal structure of an SH3 domain bound to a proline-rich motif (PRM) peptide. (PDB: 4WCI) [75]. (Right) A cartoon representation of a dense phase (green background) generated by multivalent SH3:PRM interactions. Three SH3 domains are connected by linkers in a single molecule (gray); a binding partner containing three proline-rich motifs (cyan) interacts with the SH3-protein via multivalent interactions. The two protein types crosslink each other. (Middle row) Multivalency via linear polymerization. (Left) SPOP monomers dimerize and the dimers polymerize into linear structures. The BACK dimerization domain is shown in cyan, the BTB dimerization domain in magenta, and the MATH substrate binding domain in yellow. The curved arrow indicates a 90° rotation of a SPOP dimer onto its side. (Right) SPOP oligomers bind several DAXX molecules via their MATH domains, giving rise to “brush-like” structures. These brushes are crosslinked via DAXX interactions [16,30]. (Bottom row) Local order in a liquid dense phase. The distances between NPM1 pentamers (magenta) repeat (left), giving rise to locally ordered arrays of Npm1 molecules within the dense phase. Npm1 molecules are crosslinked by arginine-rich peptides (not shown). (Right) Over greater distances, the anisotropic arrangement of arrays (each shown in different colors) gives rise to global disorder and liquid-like behavior [28].