2X36

Structure of the proteolytic domain of the Human Mitochondrial Lon protease

2X36 の概要

• エントリーDOI: 10.2210/pdb2x36/pdb
• 分子名称: LON PROTEASE HOMOLOG, MITOCHONDRIAL (2 entities in total)
• 機能のキーワード: hydrolase, catalytic dyad, transit peptide, mitochondria
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion matrix: P36776
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 134554.30

構造登録者

Garcia, J.,Ondrovicova, G.,Blagova, E.,Levdikov, V.M.,Bauer, J.A.,Kutejova, E.,Wilkinson, A.J.,Wilson, K.S. (登録日: 2010-01-21, 公開日: 2010-05-19, 最終更新日: 2023-12-20)

主引用文献

Garcia-Nafria, J.,Ondrovicova, G.,Blagova, E.,Levdikov, V.M.,Bauer, J.A.,Suzuki, C.K.,Kutejova, E.,Wilkinson, A.J.,Wilson, K.S.
Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.
Protein Sci., 19:987-, 2010

PubMed Abstract: ATP-dependent proteases are crucial for cellular homeostasis. By degrading short-lived regulatory proteins, they play an important role in the control of many cellular pathways and, through the degradation of abnormally misfolded proteins, protect the cell from a buildup of aggregates. Disruption or disregulation of mammalian mitochondrial Lon protease leads to severe changes in the cell, linked with carcinogenesis, apoptosis, and necrosis. Here we present the structure of the proteolytic domain of human mitochondrial Lon at 2 A resolution. The fold resembles those of the three previously determined Lon proteolytic domains from Escherichia coli, Methanococcus jannaschii, and Archaeoglobus fulgidus. There are six protomers in the asymmetric unit, four arranged as two dimers. The intersubunit interactions within the two dimers are similar to those between adjacent subunits of the hexameric ring of E. coli Lon, suggesting that the human Lon proteolytic domain also forms hexamers. The active site contains a 3(10) helix attached to the N-terminal end of alpha-helix 2, which leads to the insertion of Asp852 into the active site, as seen in M. jannaschii. Structural considerations make it likely that this conformation is proteolytically inactive. When comparing the intersubunit interactions of human with those of E. coli Lon taken with biochemical data leads us to propose a mechanism relating the formation of Lon oligomers with a conformational shift in the active site region coupled to a movement of a loop in the oligomer interface, converting the proteolytically inactive form seen here to the active one in the E. coli hexamer.

PubMed: 20222013
DOI: 10.1002/PRO.376

実験手法

X-RAY DIFFRACTION (2 Å)