Motif, interaction

So far ten catalytically active caspases have been reported in mouse (caspase-1, -2, -3, -6, -7, -8, -9, -11, -12,-14) and eleven in human (caspase-1, -2, -3, -4, -5, -6, -7, -8, -9, -10, -14) (Fig. 1). Caspases are expressed as inactive proenzymes that contain an amino-terminal prodomain of variable length followed by two domains with conserved sequences a large subunit ( 20 kDa, p20) and a small carboxy-terminal subunit ( 10 kDa, plO). Caspases can be divided according to absence (-3, -6, -7, -14) or presence (-1, -2, -8, -9, -10, -11, -12) of an extended prodomain containing protein-protein interaction motifs belonging to the death domain (DD) superfamily, in particular the death effector domains (DED) and the caspase activation and recruitment domains (CARD). 

Death domain (DD) superfamily consists of structurally related homotypic interaction motifs of approximately 90 amino acids. The motifs are organized in six antiparallel amphipathic a-helices, the so-called DD fold. The four members of the super family are the death domain (DD), the death effector domain (DED), the caspase activation and recruitment domain (CARD), and the Pyrin domain. All are important mediators for the assembly of caspase activating complexes. 

Formation of a novel binding site novel complexes may be formed between a SUMOylated protein and an effector protein that contains a SUMO-interacting motif (SIM or SBM). Proteins that contain two binding sites, a SIM and a weak binding motif to protein X, will bind more strongly to this protein if it is SUMOylated (Fig. 3b). Short peptides that contain the hydrophobic core motif [V/I]-X-[V/I]-[V/I] or [V/I-[V/I]]-X-[V/I] can act as a SIM and bind to SUMO. This core is often flanked by acidic amino acids and/or serine residues. 

The third signalling pathway of TRIF utilises its C-terminus. This region contains a RJQP homology interaction motif (RHIM) that binds RJQP-1 and REP-3. RIP-1 phosphorylates IKK-(3 and the NFkB pathway can be activated. REP-3 is a negative regulator of TREF competing for REP-1 [2]. 

Other Protein-Protein Interaction Motifs in RING finger Proteins... 

In addition to containing protein-protein interaction motifs, E3-substrate specificity may be affected by post-translational modifications. In particular, phosphorylation can alter E3-substrate interactions. One example is p53 where certain phosphorylations inhibit its direct binding to Mdm2, while others indirectly enhance their association by promoting nuclear localization of p53 [104-106]. Phosphorylation also directly enhances substrate interactions, as exemplified by the Cbls, which include phospho-tyrosine binding domains (see below) [107]. 

Hofmann, K. and Falquet, L. A ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems. Trends Biochem Sci 2001, 26, 347-50. 

Figure 2. Structural and functional domains of PARP-1. PARP-1 has a highly conserved structural and functional organization including (1) an N-terminal DNA binding domain with two Cys-Cys-His-Cys zinc finger motifs (FI and Fll), (2) a nuclear localization signal (NLS), (3) a central automodification domain containing a BRCT ( BRCAl C-terminus-like ) protein-protein interaction motif, and (4) a C-terminal catalytic domain with a contiguous 50 amino acid sequence, the PARP signature motif, that forms the active site...

A recent study showed that several APC substrates contain a motif comprising threonine (T), glutamate (E), and lyinse (K) residues that has been termed the TEK-box. " A similar TEK-box is also present around Lysl 1 of uhiquitin. The TEK-box is believed to be a new interaction motif critical for recognizing APC substrates for ubiquitination. It is important to note that TEK-box-containing substrates receive a Kll uhiquitin linkage as... 

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