TY - JOUR
T1 - Lipid nanotechnologies for structural studies of membrane-associated clotting proteins by cryo-electron microscopy
AU - Stoilova-McPhie, Svetla
N1 - Funding Information:
SSM acknowledges all her co-authors, former group members, mentors, and supervisors. SSM acknowledges the Sealy Center for Structural Biology at the University of Texas Medical Branch at Galveston, TX, USA, and the National Center for Molecular Imaging at Baylor College of Medicine, Houston, TX, USA, and the respective directors: Professors B. Montgomery Pettitt and Wah Chiu for continuous support. SSM acknowledges the British Heart Foundation, the American Heart Association, The University of Texas Medical Branch, and John Sealy Foundation at Galveston, TX, USA, for funding.
Publisher Copyright:
© 2017 Walter de Gruyter GmbH, Berlin/Boston.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Biological membranes surround all living cells, confining internal organelles and participating in a variety of essential cellular functions, such as signaling, electrolyte balance, and energy conversion. Cell membranes are structurally and chemically heterogeneous environment composed of numerous types of lipids arranged as a continuous bilayer. The assembly of protein complexes at the membrane surface is responsible for fundamental biological processes such as synaptic transmission, blood coagulation, and apoptosis. Resolving the macromolecular organization of these complexes at the membrane surface will help to understand the structural basis of their function and significance for the associated biological processes. In this review, we present our work on direct structure determination of membrane-bound clotting factors, specifically factor VIII (FVIII), by cryogenic electron microscopy (CryoEM). To resolve the FVIII membrane-bound organization, we have optimized lipid nanostructures resembling the activated platelet membrane. Combining structural CryoEM, capable of near-atomic resolution, with customized lipid nanotechnologies is a powerful approach to investigate how the cellular membrane can modulate protein function at close to physiological conditions. The outcome will open novel avenues for developing lipid nanotechnologies of diverse shapes and composition that can be optimized for various protein systems, germane for both drug delivery and macromolecular structure determination.
AB - Biological membranes surround all living cells, confining internal organelles and participating in a variety of essential cellular functions, such as signaling, electrolyte balance, and energy conversion. Cell membranes are structurally and chemically heterogeneous environment composed of numerous types of lipids arranged as a continuous bilayer. The assembly of protein complexes at the membrane surface is responsible for fundamental biological processes such as synaptic transmission, blood coagulation, and apoptosis. Resolving the macromolecular organization of these complexes at the membrane surface will help to understand the structural basis of their function and significance for the associated biological processes. In this review, we present our work on direct structure determination of membrane-bound clotting factors, specifically factor VIII (FVIII), by cryogenic electron microscopy (CryoEM). To resolve the FVIII membrane-bound organization, we have optimized lipid nanostructures resembling the activated platelet membrane. Combining structural CryoEM, capable of near-atomic resolution, with customized lipid nanotechnologies is a powerful approach to investigate how the cellular membrane can modulate protein function at close to physiological conditions. The outcome will open novel avenues for developing lipid nanotechnologies of diverse shapes and composition that can be optimized for various protein systems, germane for both drug delivery and macromolecular structure determination.
KW - blood coagulation factors
KW - cryo-electron microscopy
KW - lipid nanotechnologies
KW - macromolecular structure
KW - membrane-associated proteins
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U2 - 10.1515/ntrev-2016-0066
DO - 10.1515/ntrev-2016-0066
M3 - Review article
AN - SCOPUS:85015265134
SN - 2191-9089
VL - 6
SP - 127
EP - 137
JO - Nanotechnology Reviews
JF - Nanotechnology Reviews
IS - 1
ER -