Regulation of cellular events requires temporal and spatial assembly and disassembly of protein-protein interactions. Control of these complex processes is often achieved through modification-dependent binding and activation. In particular, phosphorylation and sulfatation are considered to be involved. Proteins are not just linear amino acid sequences but rather consist of characteristic globular domains that also exert specific functions in protein-protein interaction. These modular domains are regions of proteins that are stable and foldable on their own, and they are characterized by a specific structure, amino acid sequence, or both. There are now up to 733 distinct domains described in the SMART database (smart.embl-heidelberg.de) for a variety of organisms ranging from prokaryotes to eukaryotes. Similarly, the Pfam database (www.sanger.ac.uk/Software/Pfam/) lists at least one characteristic domain associated with 75% of all proteins in Arabidopsis.
Before the so-called SH2 domain was discovered as the first phosphotyro-sine binding domain, phosphorylation was thought to directly regulate protein activity through allosteric changes in protein structure and activity. Since then, the perception has changed to a view where important protein-protein interactions in cell signaling are frequently mediated by short, unstructured sequences, which specifically interact with peptide motif binding domains (Pawson and Scott 1997). Thus, phosphorylation also functions as a direct regulatory switch for protein-protein interactions.
Typical well-known examples from the mammalian field are the binding of tyrosyl-phosphorylated peptides to proteins containing Src homology domain 2 (SH2) or phosphotyrosyl binding (PTB) domain (Pawson and Gish 1992). Since the discovery of interactions of 14-3-3 proteins with characteristic peptide motifs around phosphoserine and phosphothreonine residues, the concept of phosphorylation-dependent protein-protein interactions is no longer only considered valid for phosphotyrosine, but also for phospho-rylation in general. Regulatory binding of 14-3-3 proteins to characteristic phosphorylation sites in plant proteins has been well described for nitrate re-ductase (Atwal et al. 1998), sucrose phosphate synthase (Huber and Huber 1996), and the plasma membrane ATPases (Fuglsang et al. 1999; Toroser et al. 1998). Additional phosphoserine and phosphothreonine binding domains have since been discovered: WW domains, FHA domains, WD40 repeats, the Polo box domain, and BRCT repeats. These domains have also been characterized in plant proteins.
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