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TitleHybrid Structural Analysis of the Arp2/3 Regulator Arpin Identifies Its Acidic Tail as a Primary Binding Epitope.
Journal, issue, pagesStructure, Vol. 24, Issue 2, Page 252-260, Year 2016
Publish dateFeb 2, 2016
AuthorsSusan Fetics / Aurélien Thureau / Valérie Campanacci / Magali Aumont-Nicaise / Irène Dang / Alexis Gautreau / Javier Pérez / Jacqueline Cherfils /
PubMed AbstractArpin 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 ...Arpin 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.
External linksStructure / PubMed:26774128
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution1.859 Å
Structure data

SASDBT2: Ankyrin repeat domains from human Tankyrase-2 (489-649)
Method: SAXS/SANS

SASDBU2: Human Arpin (isoform 1) (Human Arpin)
Method: SAXS/SANS

SASDBV2: Zebrafish Arpin (Zebrafish (Danio rerio) Arpin, Arpin)
Method: SAXS/SANS

SASDBW2: Zebrafish (Danio rerio) Arpin truncated C-terminal mutant (delta-C 16).
Method: SAXS/SANS

SASDBX2: Zebrafish Arpin in complex with the ankyrin repeat domains of human Tankyrase 2 (489-469)
Method: SAXS/SANS

PDB-4z68:
Hybrid structural analysis of the Arp2/3 regulator Arpin identifies its acidic tail as a primary binding epitope
Method: X-RAY DIFFRACTION / Resolution: 1.859 Å

Chemicals

ChemComp-SO4:
SULFATE ION

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • Danio rerio (zebrafish)
  • Danio rerio / homo sapiens
KeywordsPROTEIN BINDING / cell migration / Arpin / Arp 2/3 / actin polymerization

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