Cysteine-rich motif

Saha, V., et al., The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AFIO, and MLLT6 proteins. Proc Natl Acad Sci USA, 1995, 92(21), 9737-41. 

The Cl domain includes ca. 50 amino acids and contains a cysteine-rich motif with two bound + ions. In many isoenzymes, two copies of the Cl domain are present, known as CIA and CIB (or also as Cysl- and Cys2 elements). When expressed in the isolated form, both Cl domains can specifically bind phorbol esters, whereas in vivo only one of the two binding sites is occupied by phorbol esters. 

Fig. 9. Structures of soluble fragments of retrovirus TM proteins. Murine leukemia virus (MLV Fass et al, 1996) and filovirus (Weissenhom et al, 1998 Malashkevich et at, 1999) TM subunits are represented on the left by the HTLV TM structure (Kobe et at, 1999), with which they share remarkable similarity. Human and simian lentivirus TM subunits (Weissenhom etat, 1997 Chan etat, 1997 Caffrey etat, 1998) are represented by the structure of SIV TM on the right. Both structures are hairpins containing central three-stranded coiled coils surrounded by buttressing regions that pack into the grooves on the outsides of the coiled coils. The amino acid side chains in the conserved cysteine-rich motif of HTLV TM are shown as space-filling atoms and labeled according to their positions in the motif.

The cytoplasmic domains of all of these receptors have an intrinsic protein tyrosine kinase activity, and all the receptors have hydrophobic transmembrane sequences. Their extracellular regions are more variable in stmcture. Depending on the receptor, they may contain a range of domains, including (1) immrmoglobulin domains, (2) cysteine-rich motifs, (3) fibronectin type III repeats, and (4) EGF motifs. These can be present singly or in different combinations. Growth factor receptors are therefore examples of mosaic proteins. 

The major surface coat component of Toxocara larvae runs as a set of four closely migrating bands with apparent mobility of 120 kDa on SDS-PAGE. One of these was cloned and sequenced, identified as a serine-rich mucin and designated MUC-1 (Gems and Maizels, 1996). We have now established that there are at least five distinct mucin genes in this parasite, which bear general similarity but important distinctions. Thus, MUC-2, MUC-3, MUC-4 and MUC-5 are all threonine-rich rather than serine-rich, and all five differ in the repeat motifs within the mucin domains. All have similar non-mucin, cysteine-rich domains originally termed NC6 (nematode six-cysteine) domains, and since renamed SXC (six-cysteine), as described below. All mucins have a pair of SXC domains at their C-terminus, while MUC-3 and MUC-5 also have paired N-terminal SXC domains. 

The extracellular domain of RPTKs can be composed of different structural motifs. For instance, the EGFR extracellular domain contains two cysteine-rich regions. The PDGFR extracellular domain consists of five immuno-globulin-like repeats. Other domains found in the extracellular region of RPTKs include fibronectin III repeats,... 

The most extensively studied TRIAD is Parkin, shown schematically in Figure 4.5A. The N-terminus contains a region homologous to ubiquitin called the ubiq-uitin domain (UbD), which interacts directly with proteasomes. The C-terminus contains two RING fingers (Rl, R2) separated by a cysteine-rich in-between i ING (IBR) region. This TRIAD motif mediates E3 activity and interacts with molecular chaperones. The last three amino acids of Parkin interact with a PDZ domain and possibly function to anchor Parkin to lipid microdomains. 

The hypA proteins are small proteins of between 109 and 121 residnes. They are cysteine rich (e.g. nine cysteinyl residnes in the E. coli example) only font cysteinyl residues are conserved throughont all examples. These are arranged into two -cys-X-X-cys- motifs which suggests that these proteins may be redox proteins potentially... 

Synaptic exocytosis involves three SNARE proteins the R-SNARE synaptobrevin/VAMP (isoforms 1 and 2) on the vesicle, and the Q-SNAREs syntaxin (isoforms 1 and 2) and SNAP-25 on the plasma membrane (Figure 4). Since SNAP-25 has two SNARE-motifs, synaptobrevin, syntaxin, and SNAP-25 together have four SNARE-motifs. Synaptobrevins and SNAP-25 are relatively simple SNARE proteins that are composed of little else besides SNARE motifs and membrane-attachment sequences (a transmembrane region for synaptobrevin, and a cysteine-rich palmitoylated sequence for SNAP-25). Syntaxins, in contrast, are complex proteins. The N-terminal two-thirds of syntaxins include a separate, autonomously folded domain (the so-called Habc-domain), while the C-terminal third is composed of a SNARE motif and transmembrane region just like synaptobrevin. 

Fig. 1. Predicted membrane-spanning topology for mechanosensitive channels found in eukaryotes (TRPV, K2P, and DEG/ENaC channels) and bacteria (MscL and MscS). In addition to the transmembrane helices (represented as cylinders), other motifs present in these channels are designated as follows. The TRPV channels contain several cytoplasmic ankyrin domains (A) at the N terminus, and one pore-forming loop (P). K2P channels have two pore-forming loops and a self-interaction domain (SID) through which dimers are generated. DEG/ENaC sodium channels have a single pore-forming loop and three cysteine-rich domains (CRDs).

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