6X91

Crystal structure of MBP-fused human APOBEC1

Summary for 6X91

• Entry DOI: 10.2210/pdb6x91/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltodextrin-binding protein, C->U-editing enzyme APOBEC-1 chimera, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ZINC ION, ... (4 entities in total)
• Functional Keywords: apobec, rna editing, deamination, metalloenzyme, hydrolase
• Biological source: Escherichia coli; More
• Total number of polymer chains: 8
• Total formula weight: 542997.84

Authors

Wolfe, A.D.,Li, S.-X.,Chen, X.S. (deposition date: 2020-06-02, release date: 2020-12-09, Last modification date: 2023-10-18)

Primary citation

Wolfe, A.D.,Li, S.,Goedderz, C.,Chen, X.S.
The structure of APOBEC1 and insights into its RNA and DNA substrate selectivity.
NAR Cancer, 2:zcaa027-zcaa027, 2020

PubMed Abstract: APOBEC1 (APO1), a member of AID/APOBEC nucleic acid cytosine deaminase family, can edit apolipoprotein B mRNA to regulate cholesterol metabolism. This APO1 RNA editing activity requires a cellular cofactor to achieve tight regulation. However, no cofactors are required for deamination on DNA by APO1 and other AID/APOBEC members, and aberrant deamination on genomic DNA by AID/APOBEC deaminases has been linked to cancer. Here, we present the crystal structure of APO1, which reveals a typical APOBEC deaminase core structure, plus a unique well-folded C-terminal domain that is highly hydrophobic. This APO1 C-terminal hydrophobic domain (A1HD) interacts to form a stable dimer mainly through hydrophobic interactions within the dimer interface to create a four-stranded β-sheet positively charged surface. Structure-guided mutagenesis within this and other regions of APO1 clarified the importance of the A1HD in directing RNA and cofactor interactions, providing insights into the structural basis of selectivity on DNA or RNA substrates.

PubMed: 33094286
DOI: 10.1093/narcan/zcaa027

Experimental method

X-RAY DIFFRACTION (3.51 Å)