The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
Functional site class:
Arp2/3 binding motif Ligand
Functional site description:
A hydrophobic motif present in WASP family of proteins. It acts as an autoinhibitory element by binding to the GTP- binding domain, thus keeping the protein in an inhibited state. When released it contributes to actin filament nucleation by interactions with the Arp2/3 complex.
ELM Description:
This motif is found in the WASP, N-WASP and SCAR proteins mediating binding to the Arp2/3 complex, but also in WASP and N-WASP proteins intramolecularly to the GBD domain. SCAR proteins do not contain a GBD domain and therefore do not form an intramolecular inhibitory C-helix interaction, and function solely as an Arp2/3 complex motif. It is unstructured in solution although upon interaction, it forms an amphipatic α-helix. Binding occurs via hydrophobic residues found in positions 1, 5, 8 and 9 (although 8 can also be alanine). The most conserved residue is arginine in position 12, though in some cases it may also be substituted by lysine.
Pattern: [ILMV]...[ILMVF]..[ILMVA][ILMVA].[KR]R..[ILMVA]
Pattern Probability: 0.0000033
Present in taxon: Eukaryota
Interaction Domain:
PBD (PF00786) P21-Rho-binding domain (Stochiometry: 1 : 1)
o See 4 Instances for LIG_GBD_WASP_1
o Abstract
The Arp2/3 complex binding LIG_GBD_WASP_1 motif, also known as the "C- helix" (from cofilin- homology domain), is found in the C-terminus VCA region of the WASP family (comprising WASP, N-WASP and SCAR proteins). It forms an amphipathic helix mediating binding both intramolecularly with the GBD (GTPase- binding domain), acting as an autoinhibitory element, and intermolecularly with the Arp2/3 complex. It is likely that the C-helix fits in the Arp3 barbed end groove [Ti,2011] yet this statement requires to be validated experimentally.
In the absence of Cdc42, the GBD domain-binding partner, the protein exists in an auto-inhibited state with the C-helix bound to the GBD domain. Upon co-localisation with Cdc42, the GBD domain binds Cdc42, releasing the C-helix. The C-helix is then available to bind to the Arp2/3 complex and the WASP protein becomes activated. The interaction with the Arp2/3complex leads to nucleation of new actin filaments. This functional outcome is mediated by co-operative use of distinct motifs within the VCA domain. The V region (described as the WH2 motif) is responsible for actin recruitment, while the CA region (comprising the C-helix and an acidic region) cooperatively bind to the Arp2/3 complex.
o 5 selected references:

o 6 GO-Terms:

o 4 Instances for LIG_GBD_WASP_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P42768 WAS
WASP_HUMAN
466 480 EGLVGALMHVMQKRSRAIHS TP 16 Homo sapiens (Human)
3 
Q92558 WASF1
WASF1_HUMAN
527 541 ERIENDVATILSRRIAVEYS TP 9 Homo sapiens (Human)
O00401 WASL
WASL_HUMAN
467 481 SGIVGALMEVMQKRSKAIHS TP 8 Homo sapiens (Human)
3 
O08816 Wasl
WASL_RAT
463 477 SGIVGALMEVMQKRSKAIHS TP 6 Rattus norvegicus (Norway rat)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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