5LUZ

Structure of Human Neurolysin (E475Q) in complex with neurotensin peptide products

5LUZ の概要

• エントリーDOI: 10.2210/pdb5luz/pdb
• 分子名称: Neurolysin, mitochondrial, PRO-ARG-ARG-PRO neurotensin fragment, ZINC ION, ... (6 entities in total)
• 機能のキーワード: protease, mitochondria, hydrolase, neurotensin
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 164287.17

構造登録者

Masuyer, G.,Berntsson, R.P.-A.,Teixeira, P.F.,Kmiec, B.,Glaser, E.,Stenmark, P. (登録日: 2016-09-12, 公開日: 2017-12-06, 最終更新日: 2024-10-23)

主引用文献

Teixeira, P.F.,Masuyer, G.,Pinho, C.M.,Branca, R.M.M.,Kmiec, B.,Wallin, C.,Warmlander, S.K.T.S.,Berntsson, R.P.,Ankarcrona, M.,Graslund, A.,Lehtio, J.,Stenmark, P.,Glaser, E.
Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase Neurolysin.
J. Mol. Biol., 430:348-362, 2018

PubMed Abstract: Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long. The crystal structure of hNLN in complex with the products of neurotensin cleavage at 2.7Å revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. Analysis of peptide degradation in vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-β peptide, Aβ1-40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment Aβ35-40. These findings suggest that a network of proteases may be required for complete degradation of peptides localized in mitochondria.

PubMed: 29183787
DOI: 10.1016/j.jmb.2017.11.011

実験手法

X-RAY DIFFRACTION (2.7 Å)