Crystal structure of an LRR protein with two solenoids

The leucine rich repeat (LRR) is a versatile protein motif (∼20-30 amino acids) found in a variety of protein in all life forms. Tandem arrays of two or more repeats in an LRR domain form a structure similar to a horseshoe-shaped solenoid. Largely by acting as scaffolds for protein-protein interactions, LRR domains participate in diverse biological processes^1,2, as exemplified by the large family of LRR-containing receptor like kinases (LRR-RLKs) in plants³. Nearly all the known typical LRR structures comprise an N-terminal cap (LRRNT) and some of them have a C-terminal cap (LRRCT) as well, shielding the two ends of the conserved central LRR segment^1,2. An LRR domain is characterized by a repetitive sequence pattern rich in leucine residues. However, in some LRR proteins including some plant LRR-RLKs and mammalian Toll-like receptors (TLR7-9), the LRR repeats are interrupted by sequences of 30-70 residues termed island domain or non-LRR region. A recent genome-wide study identified more than 600 proteins belonging to this family of LRR proteins⁴. Compared with the canonical ones, these atypical LRR proteins are much less well-characterized structurally. BRI1 is the only atypical LRR protein whose LRR domain structure has been reported^5,6. Despite that its super-helical structure is markedly different from those of the typical LRR proteins, the interrupted LRRs in BRI1 still pack continuously, forming a single solenoid structure as observed in all the other known LRR structures. However, atypical LRRs like TLR7-9 have been predicted to form two solenoids⁷, although experimental evidence for this is lacking. Here, we describe the crystal structure of the LRR domain of TMK1 (receptor-like TransMembrane Kinase 1)⁸, an atypical LRR protein from Arabidopsis that contains two solenoids and discuss its biological implications.

TMK1 is an LRR-RLK⁸ and contains a non-LRR region in its extracellular LRR domain (TMK1-LRR) (Supplementary information, Figure S1), although its functional information is limited. We expressed TMK1-LRR (residues 1∼469) in insect cells, purified the protein as previously described⁵ and solved its crystal structure with molecular replacement. The structure was refined to a resolution of 1.55 Å with R_factor of 16.9% and R_free of 19.0% (Supplementary information, Table S1). Except for 23 residues from the N-terminus and 22 from the C-terminus, all the remaining residues were well-defined and included in the finally refined model.

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