4rqm
From Proteopedia
Crystal structure of the SeMET BICC1 SAM Domain R924E mutant
Structural highlights
DiseaseBICC1_HUMAN Autosomal dominant polycystic kidney disease. Disease susceptibility is associated with variations affecting the gene represented in this entry. FunctionBICC1_HUMAN Putative RNA-binding protein. Acts as a negative regulator of Wnt signaling. May be involved in regulating gene expression during embryonic development.[1] Publication Abstract from PubMedHead-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. Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6.,Rothe B, Leettola CN, Leal-Esteban L, Cascio D, Fortier S, Isenschmid M, Bowie JU, Constam DB Structure. 2018 Feb 6;26(2):209-224.e6. doi: 10.1016/j.str.2017.12.002. Epub 2017, Dec 28. PMID:29290488[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
