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PACSIN 1 forms tetramers via its N-terminal F-BAR domain

Halbach, Arndt; Mörgelin, Matthias LU ; Baumgarten, Maria LU ; Milbrandt, Mark; Paulsson, Mats and Plomann, Markus (2007) In The FEBS Journal 274(3). p.773-782
Abstract
The ability of protein kinase C and casein kinase 2 substrate in neurons (PACSIN)/syndapin proteins to self-polymerize is crucial for the simultaneous interactions with more than one Src homology 3 domain-binding partner or with lipid membranes. The assembly of this network has profound effects on the neural Wiskott-Aldrich syndrome protein-mediated attachment of the actin polymerization machinery to vesicle membranes as well as on the movement of the corresponding vesicles. Also, the sensing of vesicle membranes and/or the induction of membrane curvature are more easily facilitated in the presence of larger PACSIN complexes. The N-terminal Fes-CIP homology and Bin-Amphiphysin-Rvs (F-BAR) domains of several PACSIN-related proteins have... (More)
The ability of protein kinase C and casein kinase 2 substrate in neurons (PACSIN)/syndapin proteins to self-polymerize is crucial for the simultaneous interactions with more than one Src homology 3 domain-binding partner or with lipid membranes. The assembly of this network has profound effects on the neural Wiskott-Aldrich syndrome protein-mediated attachment of the actin polymerization machinery to vesicle membranes as well as on the movement of the corresponding vesicles. Also, the sensing of vesicle membranes and/or the induction of membrane curvature are more easily facilitated in the presence of larger PACSIN complexes. The N-terminal Fes-CIP homology and Bin-Amphiphysin-Rvs (F-BAR) domains of several PACSIN-related proteins have been shown to mediate self-interactions, whereas studies using deletion mutants derived from closely related proteins led to the view that oligomerization depends on the formation of a trimeric complex via a coiled-coil region present in these molecules. To address whether the model of trimeric complex formation is applicable to PACSIN 1, the protein was recombinantly expressed and tested in four different assays for homologous interactions. The results showed that PACSIN 1 forms tetramers of about 240 kDa, with the self-interaction having a K-D of 6.4 x 10(-8) M. Ultrastructural analysis of these oligomers after negative staining showed that laterally arranged PACSIN molecules bind to each other via a large globular domain and form a barrel-like structure. Together, these results demonstrate that the N-terminal F-BAR domain of PACSIN 1 forms the contact site for a tetrameric structure, which is able to simultanously interact with multiple Src homology 3 binding partners. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
PACSIN 1, syndapin 1, oligomerization, F-BAR domain, membrane
in
The FEBS Journal
volume
274
issue
3
pages
773 - 782
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000243562700016
  • scopus:33846420997
ISSN
1742-464X
DOI
10.1111/j.1742-4658.2006.05622.x
language
English
LU publication?
yes
id
2db0553e-0da4-4ae5-a6e0-9d40aa61898e (old id 676657)
date added to LUP
2007-12-07 14:52:32
date last changed
2017-01-01 07:20:04
@article{2db0553e-0da4-4ae5-a6e0-9d40aa61898e,
  abstract     = {The ability of protein kinase C and casein kinase 2 substrate in neurons (PACSIN)/syndapin proteins to self-polymerize is crucial for the simultaneous interactions with more than one Src homology 3 domain-binding partner or with lipid membranes. The assembly of this network has profound effects on the neural Wiskott-Aldrich syndrome protein-mediated attachment of the actin polymerization machinery to vesicle membranes as well as on the movement of the corresponding vesicles. Also, the sensing of vesicle membranes and/or the induction of membrane curvature are more easily facilitated in the presence of larger PACSIN complexes. The N-terminal Fes-CIP homology and Bin-Amphiphysin-Rvs (F-BAR) domains of several PACSIN-related proteins have been shown to mediate self-interactions, whereas studies using deletion mutants derived from closely related proteins led to the view that oligomerization depends on the formation of a trimeric complex via a coiled-coil region present in these molecules. To address whether the model of trimeric complex formation is applicable to PACSIN 1, the protein was recombinantly expressed and tested in four different assays for homologous interactions. The results showed that PACSIN 1 forms tetramers of about 240 kDa, with the self-interaction having a K-D of 6.4 x 10(-8) M. Ultrastructural analysis of these oligomers after negative staining showed that laterally arranged PACSIN molecules bind to each other via a large globular domain and form a barrel-like structure. Together, these results demonstrate that the N-terminal F-BAR domain of PACSIN 1 forms the contact site for a tetrameric structure, which is able to simultanously interact with multiple Src homology 3 binding partners.},
  author       = {Halbach, Arndt and Mörgelin, Matthias and Baumgarten, Maria and Milbrandt, Mark and Paulsson, Mats and Plomann, Markus},
  issn         = {1742-464X},
  keyword      = {PACSIN 1,syndapin 1,oligomerization,F-BAR domain,membrane},
  language     = {eng},
  number       = {3},
  pages        = {773--782},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {The FEBS Journal},
  title        = {PACSIN 1 forms tetramers via its N-terminal F-BAR domain},
  url          = {http://dx.doi.org/10.1111/j.1742-4658.2006.05622.x},
  volume       = {274},
  year         = {2007},
}