Details

Autor(en) / Beteiligte

• Rothé, Benjamin
• Leettola, Catherine N.
• Leal-Esteban, Lucia
• Cascio, Duilio
• Fortier, Simon
• Isenschmid, Manuela
• Bowie, James U.
• Constam, Daniel B.

Titel

Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6

Ist Teil von

• Structure (London), 2018-02, Vol.26 (2), p.209-224.e6

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Head-to-tail polymers of sterile alpha motifs (SAM) can scaffold large macromolecular complexes. Several SAM-domain proteins that bind each other are mutated in patients with cystic kidneys or laterality defects, including the Ankyrin (ANK) and SAM domain-containing proteins ANKS6 and ANKS3, and the RNA-binding protein Bicc1. To address how their interactions are regulated, we first determined a high-resolution crystal structure of a Bicc1-SAM polymer, revealing a canonical SAM polymer with a high degree of flexibility in the subunit interface orientations. We further mapped interactions between full-length and distinct domains of Bicc1, ANKS3, and ANKS6. Neither ANKS3 nor ANKS6 alone formed macroscopic homopolymers in vivo. However, ANKS3 recruited ANKS6 to Bicc1, and the three proteins together cooperatively generated giant macromolecular complexes. Thus, the giant assemblies are shaped by SAM domains, their flanking sequences, and SAM-independent protein-protein and protein-mRNA interactions. [Display omitted] •Crystal structure of the Bicc1 SAM homopolymer reveals an unusually high flexibility•ANKS3, through its C-terminal domain, disperses polymeric Bicc1 foci•ANKS6 associates with Bicc1 via ANKS3 to rescue macromolecular complexes assembly•Bicc1, ANKS3, and ANKS6 associate in a mesh-like network through multiple interfaces Rothé et al. describe how ciliopathy-associated proteins Bicc1, ANKS3, and ANKS6 assemble in a mesh-like structure scaffolded by SAM heteropolymers and additional interfaces. These interactions remodel Bicc1 foci size. While ANKS3 disperses them via its C-terminal domain, they can be rescued by recruitment of ANKS6 or a Bicc1 target mRNA.