4AD9

Crystal structure of human LACTB2.

4AD9 の概要

• エントリーDOI: 10.2210/pdb4ad9/pdb
• 分子名称: BETA-LACTAMASE-LIKE PROTEIN 2, ZINC ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: hydrolase, metallo-beta lactamase, mitochondria
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion matrix : Q53H82
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 198665.54

構造登録者

Allerston, C.K.,Krojer, T.,Shrestha, B.,Burgess Brown, N.,Chalk, R.,Elkins, J.M.,Filippakopoulos, P.,Pike, A.C.W.,Muniz, J.R.C.,Vollmar, M.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Bountra, C.,von Delft, F.,Gileadi, O. (登録日: 2011-12-22, 公開日: 2012-02-01, 最終更新日: 2024-05-08)

主引用文献

Allerston, C.K.,Gileadi, O.,Levy, S.,Liveanu, V.,Rohana, M.,Schuster, G.
Identification of Lactb2, a Metallo-Beta-Lactamase Protein, as a Human Mitochondrial Endoribonuclease
Nucleic Acids Res., 44:1813-, 2016

PubMed Abstract: Post-transcriptional control of mitochondrial gene expression, including the processing and generation of mature transcripts as well as their degradation, is a key regulatory step in gene expression in human mitochondria. Consequently, identification of the proteins responsible for RNA processing and degradation in this organelle is of great importance. The metallo-β-lactamase (MBL) is a candidate protein family that includes ribo- and deoxyribonucleases. In this study, we discovered a function for LACTB2, an orphan MBL protein found in mammalian mitochondria. Solving its crystal structure revealed almost perfect alignment of the MBL domain with CPSF73, as well as to other ribonucleases of the MBL superfamily. Recombinant human LACTB2 displayed robust endoribonuclease activity on ssRNA with a preference for cleavage after purine-pyrimidine sequences. Mutational analysis identified an extended RNA-binding site. Knockdown of LACTB2 in cultured cells caused a moderate but significant accumulation of many mitochondrial transcripts, and its overexpression led to the opposite effect. Furthermore, manipulation of LACTB2 expression resulted in cellular morphological deformation and cell death. Together, this study discovered that LACTB2 is an endoribonuclease that is involved in the turnover of mitochondrial RNA, and is essential for mitochondrial function in human cells.

PubMed: 26826708
DOI: 10.1093/NAR/GKW050

実験手法

X-RAY DIFFRACTION (2.6 Å)