5TKM

Crystal structure of human APOBEC3B N-terminal Domain

5TKM の概要

• エントリーDOI: 10.2210/pdb5tkm/pdb
• 分子名称: DNA dC->dU-editing enzyme APOBEC-3B, ZINC ION (3 entities in total)
• 機能のキーワード: hydrolase, deaminase, apobec
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47298.28

構造登録者

Xiao, X.,Yang, H.,Arutiunian, V.,Besse, G.,Morimoto, C.,Zirkle, B.,Chen, X.S. (登録日: 2016-10-07, 公開日: 2017-06-14, 最終更新日: 2023-10-04)

主引用文献

Xiao, X.,Yang, H.,Arutiunian, V.,Fang, Y.,Besse, G.,Morimoto, C.,Zirkle, B.,Chen, X.S.
Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation.
Nucleic Acids Res., 45:7494-7506, 2017

PubMed Abstract: The catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B. We show that (i) A3B expressed in human cells exists in hypoactive high-molecular-weight (HMW) complexes, which can be activated without apparent dissociation into low-molecular-weight (LMW) species after RNase A treatment. (ii) Multiple surface hydrophobic residues of CD1 mediate the HMW complex assembly and affect the catalytic activity, including one tryptophan residue W127 that likely acts through regulating nucleic acid binding. (iii) One of the highly positively charged surfaces on CD1 is involved in RNA-dependent attenuation of A3B catalysis. (iv) Surface hydrophobic residues of CD1 are involved in heterogeneous nuclear ribonucleoproteins (hnRNPs) binding to A3B. The structural and biochemical insights described here suggest that unique structural features on CD1 regulate the molecular assembly and catalytic activity of A3B through distinct mechanisms.

PubMed: 28575276
DOI: 10.1093/nar/gkx362

実験手法

X-RAY DIFFRACTION (1.9 Å)