7OBM

Crystal structure of the human Prolyl Endopeptidase-Like protein short form (residues 90-727)

7OBM の概要

• エントリーDOI: 10.2210/pdb7obm/pdb
• 分子名称: Prolyl endopeptidase-like (1 entity in total)
• 機能のキーワード: esterase mitochondrial beta-propeller, structural genomics, psi-2, protein structure initiative, mitochondrial protein partnership, mpp, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 73575.57

構造登録者

Rosier, K.,McDevitt, M.T.,Brendan, J.F.,Marcaida, M.J.,Bingman, C.A.,Pagliarini, D.J.,Creemers, J.W.M.,Smith, R.W.,Mitochondrial Protein Partnership (MPP) (登録日: 2021-04-22, 公開日: 2021-11-10, 最終更新日: 2024-06-19)

主引用文献

Rosier, K.,McDevitt, M.T.,Smet, J.,Floyd, B.J.,Verschoore, M.,Marcaida, M.J.,Bingman, C.A.,Lemmens, I.,Dal Peraro, M.,Tavernier, J.,Cravatt, B.F.,Gounko, N.V.,Vints, K.,Monnens, Y.,Bhalla, K.,Aerts, L.,Rashan, E.H.,Vanlander, A.V.,Van Coster, R.,Regal, L.,Pagliarini, D.J.,Creemers, J.W.M.
Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function.
Iscience, 24:103460-103460, 2021

PubMed Abstract: Deficiency of the serine hydrolase prolyl endopeptidase-like (PREPL) causes a recessive metabolic disorder characterized by neonatal hypotonia, feeding difficulties, and growth hormone deficiency. The pathophysiology of PREPL deficiency and the physiological substrates of PREPL remain largely unknown. In this study, we connect PREPL with mitochondrial gene expression and oxidative phosphorylation by analyzing its protein interactors. We demonstrate that the long PREPL isoform localizes to mitochondria, whereas PREPL remains cytosolic. KO mice showed reduced mitochondrial complex activities and disrupted mitochondrial gene expression. Furthermore, mitochondrial ultrastructure was abnormal in a PREPL-deficient patient and KO mice. In addition, we reveal that PREPL has (thio)esterase activity and inhibition of PREPL by Palmostatin M suggests a depalmitoylating function. We subsequently determined the crystal structure of PREPL, thereby providing insight into the mechanism of action. Taken together, PREPL is a (thio)esterase rather than a peptidase and PREPL is involved in mitochondrial homeostasis.

PubMed: 34888501
DOI: 10.1016/j.isci.2021.103460

実験手法

X-RAY DIFFRACTION (3.1 Å)