| Accession: | |
|---|---|
| Functional site class: | Actin-binding motifs |
| Functional site description: | The function of actin in the cell is regulated in a variety of ways, including interactions with the RPEL motifs and WH2 motifs, which bind to actin's hydrophobic cleft formed by its subdomains 1 and 3. RPEL motifs, unstructured in solution, form two helices linked by a loop upon binding. They are known to sequester MRTF transcription factors in the cytosol. RPEL-containing proteins have been found in metazoans, as well as in fungi. WH2 motifs are present in many eukaryotic organisms, including metazoa, plants and fungi. The structure of the motif comprises a short N-terminal helix of a variable length followed by an irregular region. It acts via interactions with G-actin, thus promoting or inhibiting the filament assembly. In some proteins WH2 motifs are also involved in regulation of the filament nucleation process. The differences in the functioning of various WH2-containing proteins may result from motif variants, which in several cases are not fully consistent with the assumed conservation pattern. |
| ELMs with same func. site: | LIG_Actin_RPEL_3 LIG_Actin_WH2_1 LIG_Actin_WH2_2 |
| ELM Description: | WH2 is a bipartite motif consisting of a short alpha-helix at its N-terminus followed by a disordered region. The most important amino acids determining the motif's ability to interact with actin are leucine and lysine (often substituted by arginine) in positions -4 and -3 from the motif C-terminus, respectively. The N-terminal helix is rich in hydrophobic amino acids enabling it to fit into the cleft formed by actin's subdomains 1 and 3. The helix contains a fragment of variable length (4-7 residues) that enables another helix turn to be included. It is followed by a loop, comprising the critical leucine and lysine/arginine residues interacting directly with the actin molecule. In several cases the C-terminal region is longer and contains residues forming a conserved pattern .T.[DE]...P which is putatively stabilizing WH2- actin interactions. This extension of the motif, not included in the ELM regular expression occurs in beta-thymosins, a group of proteins composed of WH2 domains only. For proper functioning they require an additional K/R residue at the C-terminus. They also contain a phenylalanine in position -5, conserved exclusively within this protein family. However, the level of conservation in these positions is too low to consider them an integral part of the motif. The WH2 motif is present in many proteins in various eukaryotes. It is possible to find several sequence variants, which differ from the assumed conservation pattern. In some proteins there are single cases of e.g. K/R substituted by T or N, yet their role and putative impact on actin binding remains unclear. WH2 motifs were divided into two groups. In this version positions 1 and 3 are not precisely defined, as many variants are found in different proteins. Despite lower level of conservation, this group of the WH2 motifs appears to demonstrate equally high actin-binding affinity. |
| Pattern: | [^R]..((.[ILMVF])|([ILMVF].))[^P][^P][ILVM].{4,7}L(([KR].)|(NK))[VATIGS] |
| Pattern Probability: | 0.0006603 |
| Present in taxon: | Eukaryota |
| Interaction Domain: |
Actin (PF00022)
Actin
(Stochiometry: 1 : 1)
PDB Structure: 2D1K
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