Leucine-rich domain

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). 

Leucine residues 2, 5, 7, 12, 20, and 24 of the motif are invariant in both type A and type B repeats of the ribonuclease inhibitor. An examination of more than 500 tandem repeats from 68 different proteins has shown that residues 20 and 24 can be other hydrophobic residues, whereas the remaining four leucine residues are present in all repeats. On the basis of the crystal structure of the ribonuclease inhibitor and the important structural role of these leucine residues, it has been possible to construct plausible structural models of several other proteins with leucine-rich motifs, such as the extracellular domains of the thyrotropin and gonadotropin receptors. 

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... 

Blake, T. J., M. Shapiro, H. C. d. Morse, and W. Y. Langdon. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif Oncogene. 6 653-657.1991. 

Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain regulation of subcellular localization and p53 activity by NES masking. EMBO J 18 1660-1672... 

Our laboratory started to work on circadian rhythms by serendipity, while studying the liver-specific transcription of the serum albumin gene. We isolated a cDN A copy for a transcription factor that we dubbed DBP (for albumin promoter D-element Binding Protein). DBP, a basic leucine zipper (bZip) transcription factor, is the founding member of the PAR (proline-acidic amino acid rich)-domain bZip transcription factors, a small subfamily of bZip proteins consisting of DBP, TEF and HLF. It turned out that DBP protein and mRNA accumulation undergo circadian cycles with amplitudes in excess of one hundred-fold (Wuarin Schibler 1990). 

Each of the monomeric proteins c-jun and c-fos, as well as other members of the leucine zipper family, has an N-terminal DNA-binding domain rich in positively charged basic amino acid side chains, an activation domain that can interact with other proteins in the initiation complex, and the leucine-rich dimerization domain.363 The parallel coiled-coil structure (Fig. 2-21) allows for formation of either homodimers or heterodimers. However, cFos alone does not bind to DNA significantly and the cjun/cFos heterodimer binds much more tightly than does cjun alone.364 The yeast transcriptional activator protein GCN4 binds to the same 5 -TGACTCA sequence as does the mammalian AP-1 and also has a leucine zipper structure.360 364 365... 

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