| Accession: | |
|---|---|
| Functional site class: | Motifs binding the TPR domain of kinesin light chain 1 |
| Functional site description: | Kinesins are important microtubule motors for binding and anterograde transport of cellular cargo such as vesicles and organelles. The conventional kinesin 1 oligomer consists of a heavy chain dimer functioning as an ATP hydrolysing motor domain and two identical light chains (KLC) containing tetratricopeptide repeat (TPR) regions for binding cellular cargo. These TPRs form rod-like structures that mediate protein interactions by recognizing and binding a variety of cargo proteins such as caytaxin and calsyntenin, proteins involved in neuronal development and maturation. Since the KLC TPR is also recruited by viral envelope and bacterial associated proteins it is also important to the life cycle of invasive pathogens. A 'WD' motif has been shown to bind the KLC1 and KLC2 TPR and thereby mediate cargo transport. More recently a second class of KLC1 isoform-specific motif, termed 'Y-acidic’ has been identified in some adaptor proteins like JIP1 and TorsinA. |
| ELMs with same func. site: | LIG_KLC1_WD_1 LIG_KLC1_Yacidic_2 |
| ELM Description: | The 'WD' motif is found in many cellular cargo proteins and is able to bind to the TPR region of the KLCs from kinesin 1. Hereby proteins such as calsyntenin, caytaxin, BNIP members and Gadkin recruit the KLC TPR to mediate active transport of molecules and vesicles in the plus-end direction along the microtubules. The motif consists of a WD or WE core often surrounded by other acidic residues. In most cases the motif also includes an L or other hydrophobic residue at two positions, one prior to the W and the other 5 or 6 residues after. The binding groove of TPR stabilises the binding motif with salt bridges and hydrogen bonds. It provides a leucine-rich pocket binding the W as well as a hydrophobic pocket holding the first L residue of the motif as shown in the crystal structure of KLC2 TPR with a peptide of SifA-kinesin interacting protein (SKIP or PKHM2; 3ZFW, Pernigo,2013). Most often, the motif is located toward C- or N-terminal regions of the cargo proteins. The motif has been associated with KLC1 and KLC2 but since the binding pocket is well-conserved it is likely to also bind other KLCs. Very often the 'WD' motif appears in pairs (bipartite) usually separated by less than 100 amino acids, suggesting cooperative function. However experimental evidence suggests that one motif can be sufficient for KLC binding. The consensus of the different 'WD' motifs could be summarised in the expression: φ[-]W[DE] [^+].{3,4}φ Besides its cellular functions, the WD motif is also involved in bacterial pathogenesis mechanisms as in the targeted host protein SKIP and is also found in various viral proteins, such as A36 and F12 in vaccinia virus. Pathogens use the motif in order to 'hijack' cellular transport mechanisms and regulate movement of bacterial vacuoles or entire viruses within the cell. |
| Pattern: | [LMTAFSRI][^KRG]W[DE].{3,5}[LIVMFPA] |
| Pattern Probability: | 0.0003538 |
| Present in taxons: | Eukaryota Poxviridae |
| Interaction Domain: |
TPR (SM00028)
Tetratricopeptide repeats.
(Stochiometry: 1 : 1)
|