Leucine-rich repeating units

The crystal structure of one LRR protein, the RNAse inhibitor, has revealed that leucine-rich repeats correspond to p-a structural units. This units are arranged for a parallel p-sheet with one surface exposed to solvent so that the protein acquires an unusual non-globular shape, which may be responsible for proteinbinding functions [57]. 

Evdokimov, A. G., Anderson, D. E., Routzahn, K. M., and Waugh, D. S. (2001). Unusual molecular architecture of the Yersinia pestis cytotoxin YopM A leucine-rich repeat protein with the shortest repeating unit./. Mol. Biol. 312, 807-821. 

Figure 35.3 PAMP-recognition unit of the Toll-like receptor. (A) The structure of the leucine-rich repeat (LRR) domain from human TLR-3. Notice that the LRR units come together to form a central parallel (3 sheet that curls to form a concave structure. (B) The structure of a single LRR showing the positions of the residues that are generally approximately conserved. Notice that the leucine residues come together to form a hydrophobic core with the single 3 strand along on one side. [Drawn from IZIW.pdb],...

How do TLRs recognize PAMPs The leucine-rich repeat domain from human TLK-3 has a remarkable structure (Figure 33.3). Kach of its LRR units contributes a single (3 strand to a large parallel p sheet that lines the inside of a concave structure. This hooklike structure immediately suggests a model for how TLRs bind PAMPs—namely, that the PAMP lies on the inside of the hook. This model is likely accurate for some TLRs. However, for other TLRs, the PAMP-binding site appears to lie on one side of the structure, and the central hole is blocked by host carbohydrates linked to the structure. 

The horseshoe structure is formed by homologous repeats of leucine-rich motifs, each of which forms a p-loop-a unit. The units are linked together such that the p strands form an open curved p sheet, like a horseshoe, with the a helices on the outside of the p sheet and the inside exposed to solvent. The invariant leucine residues of these motifs form the major part of the hydrophobic region between the a helices and the p sheet. 

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