Structural and functional studies of plant receptor kinases

Abstract

Receptor kinases (RKs) in plants play important roles in sensing intracellular and external cues to mediate cell-cell communication. RKs have a conserved tripartite structural organization, consisting of a non-conserved extracellular domain (ECD), a single membrane-spanning segment to anchor the protein within the membrane, and a conserved intracellular kinase domain. The model plant Arabidopsis encodes approximately 600 RKs, representing nearly 2.5% of the coding sequences within its entire genome. Ligand perception by the ECDs of RKs, in a direct or indirect manner, generally results in phosphorylation of their KDs, thus initiating downstream signaling. During the past decades, great progress has been made toward understanding the molecular mechanisms of how RKs are involved in multiple biological processes, such as meristem development, stomatal development, pollen tube navigation, immune response and self-incompatibility. More recently, numerous crystal structures of ECDs in free, ligand-bound and coreceptor-bound forms have been solved. These structural data, coupled with others, have provided significant insights into how RKs recognize their cognate ligands and consequently become activated at an atomic level. Most of the RK structures solved thus far belong to LRR-RKs. Structural studies showed that small peptides (with ~10−20 residues in length) from plants or pathogens bind to their LRR-RK receptors in a remarkably conserved manner, with the peptides adopting an elongated conformation to interact with the inner surfaces of LRRs. Specific recognition of a peptide is dictated by the exposed residues of its LRR receptor. As a matter of fact, the mechanism is so conserved that it has been successfully used to identify LRR-RK receptors of known small peptides. In contrast with small peptides, larger peptides with a well-defined structure are recognized by their LRR-RK receptors though varied mechanisms. An extreme example of this is EPF recognition by the LRR-RKs ERfs, in which the receptor-like protein TMM is required to perform a complex with ERfs for the recognition. Several structures of non-LRR-RKs with ligands bound were also reported. Understandably, these RKs vary significantly in their mechanisms of ligand recognition due to their non-conserved structures. But with more structures solved, ligand recognition mechanisms within the same RK subfamily may be generalized and consequently used for matching ligand-receptor pairs. A general model defined by the structural studies is that ligand-induced dimerization is required for the activation of RKs. The more common mode of dimerization is ligand-induced heterodimerization of two different RKs, with one acting as the primary receptor and other as the co-receptor. Typical examples for this include BL- and flg22-induced heterodimeric BRI1-BAK1 and FLS2-BAK1 complexes, respectively. While less frequently used, ligand-induced homodimerization of RKs has also been demonstrated for their activation, as exemplified by chitin-induced CERK1 and SCR9-induced SRK9 activation. Despite the conserved dimerization mode for activation, the mechanisms involved are diversified among RKs. Several structures revealed that heterodimerization of ligand-glued two RKs is important for their activation. In this mechanism, assembly of a signaling RK complex is sequential, in which a ligand first recognized by the primary receptor is directly involved in recruitment of a co-receptor. Most of the small plant peptides (~5−20 residues length) bound by receptors have been shown to follow this mechanism to induce RK heterodimerization. The small peptide hormone PSK, however, employs an allosteric strategy to induce heterodimerization of its receptor PSKR with coreceptor BAK1. Cross-linking of two CERK1 molecules by a chitin is required for the activation of this RK. In contrast, homodimerization of SRK9 induced by SCR9 is both ligand- and receptor mediated, resulting in formation of a 2:2 complex. Given the large number of RKs in plants, it can be anticipated that more diversity in the mechanisms of RK activation will be revealed.