Leucine-rich repeat domains LRRs

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.

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. 

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. 

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... 

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). 

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],...

Sequence motifs [33330 ANK (ANKyrin-like) repeats AAA (ATPases associated with a variety of cellular activities) domain or CAD (conserved ATPase domain) with Walker A and B motifs KEKE (motif rich in alternating lysine (K) and glutamate (E) residues) cys box of UBPs (ubiquitin-processing enzymes) nun- LRR (leucine-rich repeat)-like motif [ZD MPN (found in Mprland Padl in the N terminus) motif ISSSSSSS PCI (for proteasome, COP9andinitiation factor 3) motif H UCH (ubiquitin C-terminal hydrolases) block. 

Fig. 1 The human IAP protein family. Human IAP proteins contain one or three baculovirus IAP repeat (BIR) domains. Several IAP family members also have RING (really interesting new gene) and UBA (ubiquitin associated) domains. The c-IAPl and C-IAP2 proteins each contain a caspase recruitment domain (CARD). Survivin contains a coiled coil domain NAIP has NACHT (domain present in NAIP, CIITA, HET-E, TP1) and leucine rich repeat (LRR) domains Apollon possesses a ubiquitin conjugating (UBC) domain...

Figure 18.3 The mammalian lAP family. The distinct domains are shown for each lAP. (BIR—baculovirus lAP repeat CARD-caspase activation recruitment domain RING—really interesting new gene zinc finger LRR—leucine rich repeat NOD-nucleotide-binding oligomerization domain).

---