4z68
Hybrid structural analysis of the Arp2/3 regulator Arpin identifies its acidic tail as a primary binding epitope
Structural highlights
FunctionARPIN_HUMAN Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence.[1] Publication Abstract from PubMedArpin is a newly discovered regulator of actin polymerization at the cell leading edge, which steers cell migration by exerting a negative control on the Arp2/3 complex. Arpin proteins have an acidic tail homologous to the acidic motif of the VCA domain of nucleation-promoting factors (NPFs). This tail is predicted to compete with the VCA of NPFs for binding to the Arp2/3 complex, thereby mitigating activation and/or tethering of the complex to sites of actin branching. Here, we investigated the structure of full-length Arpin using synchrotron small-angle X-ray scattering, and of its acidic tail in complex with an ankyrin repeats domain using X-ray crystallography. The data were combined in a hybrid model in which the acidic tail extends from the globular core as a linear peptide and forms a primary epitope that is readily accessible in unbound Arpin and suffices to tether Arpin to interacting proteins with high affinity. Hybrid Structural Analysis of the Arp2/3 Regulator Arpin Identifies Its Acidic Tail as a Primary Binding Epitope.,Fetics S, Thureau A, Campanacci V, Aumont-Nicaise M, Dang I, Gautreau A, Perez J, Cherfils J Structure. 2016 Jan 5. pii: S0969-2126(15)00505-5. doi:, 10.1016/j.str.2015.12.001. PMID:26774128[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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