4RQM

Crystal structure of the SeMET BICC1 SAM Domain R924E mutant

Summary for 4RQM

• Entry DOI: 10.2210/pdb4rqm/pdb
• Related: 4RQN
• Descriptor: Protein bicaudal C homolog 1, ZINC ION (3 entities in total)
• Functional Keywords: sam domain, protein-protein interaction domain, polymerization domain, polymerization, p-bodies, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 24440.60

Authors

Leettola, C.N.,Cascio, D.,Bowie, J.U. (deposition date: 2014-11-03, release date: 2016-01-27, Last modification date: 2024-10-16)

Primary citation

Rothe, B.,Leettola, C.N.,Leal-Esteban, L.,Cascio, D.,Fortier, S.,Isenschmid, M.,Bowie, J.U.,Constam, D.B.
Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6.
Structure, 26:209-224.e6, 2018

PubMed Abstract: 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.

PubMed: 29290488
DOI: 10.1016/j.str.2017.12.002

Experimental method

X-RAY DIFFRACTION (1.75 Å)