A hinge in the distal end of the PACSIN 2 F-BAR domain may contribute to membrane-curvature sensing.
The protein kinase C and casein kinase 2 substrates in neurons (PACSINs) represent a subfamily of membrane-binding proteins characterized by an amino-terminal Bin-Amphiphysin-Rvs (F-BAR) domain. PACSINs link membrane trafficking with actin dynamics and regulate the localization of distinct cargo molecules. The F-BAR domain forms a dimer essential for lipid binding. We have obtained crystals of authentic murine PACSIN 2 that contain an ordered F-BAR domain, indicating that additional domains are flexibly connected to F-BAR. The structure shares similarity to other BAR domains and exhibits special features unique to PACSINs. These include the uneven distribution of charged residues on the concave molecular surface and a so-called wedge loop that is driven into the membrane upon binding of PACSIN. The murine PACSIN 2 F-BAR domain requires dimerization for sensing of curved membranes, and the present structure also provides a mechanism for higher-order oligomer formation. Importantly, comparison of murine with human and Drosophila PACSIN 2 F-BAR domains reveals stark differences in the orientation of distal helical segments leading to a wider crescent shape of murine PACSIN 2. We define hinge residues for these movements that may help PACSINs sense and concomitantly reinforce membrane curvature.
Plomann
Markus
M
Institute for Biochemistry II and Center for Molecular Medicine Cologne (CMMC), University of Cologne, D-50931 Cologne, Germany.
Wittmann
Julia G
JG
Rudolph
Markus G
MG
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry*; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D004331:Drosophila melanogaster; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008563:Membrane Lipids; C120714:PACSIN2 protein, human; C485644:Pacsin2 protein, mouse; D011506:Proteins; C540273:Synd protein, Drosophila