Leucine-rich repeat domains

F. 7 PARKS LRRK2 structure tuid mutations. ANK, ankyrin repeat region LRR, leucine-rich repeat domain ROC, Ras of complex COR, C-terminal of Ras (GTPase) (Tan et al., 2(X)7). Scale is approximate... 

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. 

Signaling by PKC is terminated by concentrations of its ligands dropping to basal levels (i.e., Ca2+ and diacylglycerol) and by dephosphorylation of the three processing sites. Dephosphorylation is controlled, in part, by a recently discovered hydrophobic phosphorylation motif phosphatase. This phosphatase, PHLPP (for PH domain Leucine-rich repeat Protein Phosphatase) dephosphorylates conventional and novel PKC isozymes, initiating their downregulation. 

At least 12 ditferent TLRs have so far been identified in mammals (Uematsu and Akria 2007). TLRs are type I transmembrane PRRs that possess an extracellular domain contaiiung leucine-rich repeats (LRR), a transmembrane domain, and an... 

A third myelin inhibitory protein, OMgp, is a GPI-linked protein expressed by oligodendrocytes [18], OMgp is a relatively minor component of myelin, believed to be localized to the paranodal loops, next to the node of Ranvier. OMgp contains a leucine-rich repeat (LRR) domain and a C-terminal domain with serine/threonine repeats. Like MAG, OMgp is also found in the PNS. Like Nogo, OMgp is also expressed in adult neurons. 

Fig. 2. Examples of the structures of protein domains and repeats. The images were generated using Molscript (Kraulis, 1991). (A) Immunoglobulin domain (PDB identifier ltlk) (Holden et al1992), (B) A zinc finger domain with coordinated zinc ion (PDB identifienlzaa) (Pavletich and Pabo, 1991). (C) A /3-propeller domain composed of seven WD40 repeats (PDB identifier lgp2) (Wall et al., 1995), (D) An elongated domain of variant leucine-rich repeats (PDB identifienllrv) (Peters et al., 1996).

LRRCT Leucine rich repeat C-terminal domain E(M) 0(0) 7(9) ... 

II.2f Phlpp +103 kb (il) R 1E2.1 0 PH domain and leucin rich repeat protein phosphatase, dephos phorylates Akt, promotes apoptosis, and snppresses tnmonr growth 2... 

RNA-binding activity. The other sub-domain is a leucine-rich repeat (LRR) domain. LRR does not show general RNA-binding activity, but it is required for specific binding to the CTE. Recognition of CTE... 

Figure 13.3 Domain organization of Tap. Human Tap is a 619-amino acids protein. The minimal CTE-binding domain is composed of two globular sub-domains (the ribonucleprotein or RNP domain and the leucine-rich repeat or LRR) and a flexible N-terminal region. Also shown is the localization of the C-terminal nucleocytoplasmic shuttling domain, the cargo-binding domain, and the NTF2-like domain that exhibits pi5 binding activity.

Goshima, M., K. Kariya, Y. Yamawaki-Kataoka, T. Okada, M. Shibatohge, F. Shima, E. Fujimoto, and T. Kataoka. 1999. Characterization of a novel Ras-binding protein Ce-FLI-1 comprising leucine-rich repeats and gelsolin-like domains. Biochem Biophys Res Commun. 257 111-6. 

The N-terminal region of NgR harbors eight canonical leucine rich repeats (LRR) that contain the LRR-signature sequence LxxLxLN/CxL. The NgR LRRs are flanked by a leucine rich repeat N-terminal subdomain (LRRNT) and a leucine rich repeat C-terminal subdomain (LRRCT), which are small protein motifs frequently found next to LRR domains. Binding studies reveal that the leucine rich domains are necessary and sufficient for ligand recognition (Fournier et al., 2002). 

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