期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 18, 页码 E3622-E3631出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1619806114
关键词
dimeric tubulin; protein-lipid interactions; neutron reflectometry; molecular dynamics; peripheral membrane proteins
资金
- NSF [ACI-1053575]
- NSF at the Pittsburgh Supercomputing Center (PSC) [ACI-1445606]
- NIH [R01GM116961]
- PSC
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH
- National Sciences and Engineering Research Council Discovery Grant [RGPIN-315019]
- Alberta Innovates Technology Futures Strategic Chair in (Bio) Molecular Simulation
- Direct For Computer & Info Scie & Enginr
- Office of Advanced Cyberinfrastructure (OAC) [1445606] Funding Source: National Science Foundation
Dimeric tubulin, an abundant water-soluble cytosolic protein known primarily for its role in the cytoskeleton, is routinely found to be associated with mitochondrial outer membranes, although the structure and physiological role of mitochondria-bound tubulin are still unknown. There is also no consensus on whether tubulin is a peripheral membrane protein or is integrated into the outer mitochondrial membrane. Here the results of five independent techniques-surface plasmon resonance, electrochemical impedance spectroscopy, bilayer overtone analysis, neutron reflectometry, and molecular dynamics simulations-suggest that a-tubulin's amphipathic helix H10 is responsible for peripheral binding of dimeric tubulin to biomimetic mitochondrial membranes in a manner that differentiates between the two primary lipid headgroups found in mitochondrial membranes, phosphatidylethanolamine and phosphatidylcholine. The identification of the tubulin dimer orientation and membrane-binding domain represents an essential step toward our understanding of the complex mechanisms by which tubulin interacts with integral proteins of the mitochondrial outer membrane and is important for the structure-inspired design of tubulin-targeting agents.
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