TY - JOUR
T1 - Structure and Analysis of FCHo2 F-BAR Domain
T2 - A Dimerizing and Membrane Recruitment Module that Effects Membrane Curvature
AU - Henne, William Mike
AU - Kent, Helen M.
AU - Ford, Marijn G J
AU - Hegde, Balachandra G.
AU - Daumke, Oliver
AU - Butler, P. Jonathan G
AU - Mittal, Rohit
AU - Langen, Ralf
AU - Evans, Philip R.
AU - McMahon, Harvey T.
N1 - Funding Information:
We would like to thank members of our labs for their expert advice and help in this study. This work was supported by the Medical Research Council (UK), and by an MRC Graduate Scholarship and a Trinity College External Research Studentship to W.M.H. R.L. was funded by the NIH (GM63915). We thank ESRF staff for assistance in data collection.
PY - 2007/7/18
Y1 - 2007/7/18
N2 - A spectrum of membrane curvatures exists within cells, and proteins have evolved different modules to detect, create, and maintain these curvatures. Here we present the crystal structure of one such module found within human FCHo2. This F-BAR (extended FCH) module consists of two F-BAR domains, forming an intrinsically curved all-helical antiparallel dimer with a Kd of 2.5 μM. The module binds liposomes via a concave face, deforming them into tubules with variable diameters of up to 130 nm. Pulse EPR studies showed the membrane-bound dimer is the same as the crystal dimer, although the N-terminal helix changed conformation on membrane binding. Mutation of a phenylalanine on this helix partially attenuated narrow tubule formation, and resulted in a gain of curvature sensitivity. This structure shows a distant relationship to curvature-sensing BAR modules, and suggests how similar coiled-coil architectures in the BAR superfamily have evolved to expand the repertoire of membrane-sculpting possibilities.
AB - A spectrum of membrane curvatures exists within cells, and proteins have evolved different modules to detect, create, and maintain these curvatures. Here we present the crystal structure of one such module found within human FCHo2. This F-BAR (extended FCH) module consists of two F-BAR domains, forming an intrinsically curved all-helical antiparallel dimer with a Kd of 2.5 μM. The module binds liposomes via a concave face, deforming them into tubules with variable diameters of up to 130 nm. Pulse EPR studies showed the membrane-bound dimer is the same as the crystal dimer, although the N-terminal helix changed conformation on membrane binding. Mutation of a phenylalanine on this helix partially attenuated narrow tubule formation, and resulted in a gain of curvature sensitivity. This structure shows a distant relationship to curvature-sensing BAR modules, and suggests how similar coiled-coil architectures in the BAR superfamily have evolved to expand the repertoire of membrane-sculpting possibilities.
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U2 - 10.1016/j.str.2007.05.002
DO - 10.1016/j.str.2007.05.002
M3 - Article
C2 - 17540576
AN - SCOPUS:34447256592
SN - 0969-2126
VL - 15
SP - 839
EP - 852
JO - Structure
JF - Structure
IS - 7
ER -