title: The structure of full-length human CTNNBL1 reveals a distinct member of the armadillo-repeat protein family.
abstract: Catenin-β-like protein 1 (CTNNBL1) is a highly conserved protein with multiple functions, one of which is to act as an interaction partner of the antibody-diversification enzyme activation-induced cytidine deaminase (AID) for its nuclear import and subnuclear trafficking. Here, the crystal structure of full-length human CTNNBL1 is reported. The protein contains six armadillo (ARM) repeats that pack into a superhelical ARM domain. This ARM domain is unique within the ARM protein family owing to the presence of several unusual structural features. Moreover, CTNNBL1 contains significant and novel non-ARM structures flanking both ends of the central ARM domain. A strong continuous hydrophobic core runs through the whole structure, indicating that the ARM and non-ARM structures fold together to form an integral structure. This structure defines a highly restrictive and discriminatory protein-binding groove that is not observed in other ARM proteins. The presence of a cluster of histidine residues in the groove implies a pH-sensitive histidine-mediated mechanism that may regulate protein binding activity. The many unique structural features of CTNNBL1 establish it as a distinct member of the ARM protein family. The structure provides critical insights into the molecular interactions between CTNNBL1 and its protein partners, especially AID.
authors.affiliation: Department of Computer Science, Southern Illinois University, 1000 Faner Drive, Carbondale, IL 62901, USA.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Huang
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Du
mesh_terms: D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry* / Q000378:metabolism*; D051186:Armadillo Domain Proteins / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003564:Cytidine Deaminase / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D051017:Apoptosis Regulatory Proteins; D051186:Armadillo Domain Proteins; C479429:CTNNBL1 protein, human; D009687:Nuclear Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; CTNNBL1; armadillo repeat; nuclear import