NMR structure and MD simulations of the AAA protease intermembrane space domain indicates peripheral membrane localization within the hexaoligomer.
We have determined the solution NMR structure of the intermembrane space domain (IMSD) of the human mitochondrial ATPase associated with various activities (AAA) protease known as AFG3-like protein 2 (AFG3L2). Our structural analysis and molecular dynamics results indicate that the IMSD is peripherally bound to the membrane surface. This is a modification to the location of the six IMSDs in a model of the full length yeast hexaoligomeric homolog of AFG3L2 determined at low resolution by electron cryomicroscopy [1]. The predicted protein-protein interaction surface, located on the side furthest from the membrane, may mediate binding to substrates as well as prohibitins.
Department of Chemistry and Biochemistry, Northeast Structural Genomics Consortium, Miami University, Oxford, OH 45056, USA. Electronic address: theresa.ramelot@miamiOH.edu.
Theresa A
TA
Ramelot
Yunhuang
Y
Yang
Indra D
ID
Sahu
Hsiau-Wei
HW
Lee
Rong
R
Xiao
Gary A
GA
Lorigan
Gaetano T
GT
Montelione
Michael A
MA
Kennedy
D049069:ATP-Dependent Proteases / Q000737:chemistry* / Q000378:metabolism; D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D020285:Cryoelectron Microscopy; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D055503:Protein Multimerization
D049069:ATP-Dependent Proteases; C120699:AFG3L2 protein, human; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities
Molecular dynamics; NMR structure; m-AAA protease