SNX33 (sorting nexin 33) is a homologue of the endocytic prote-in SNX9 and has been implicated in actin polymerization and the endocytosis of the amyloid precursor protein. SNX33 belongs to the large family of BAR (Bin/amphiphysin/Rvs) domain-containing proteins, which alter cellular protein trafficking by modulating cellular membranes and the cytoskeleton. Some BAR domains engage in homodimerization, whereas other BAR domains also mediate heterodimerization between different BAR domain-containing proteins. The molecular basis for this difference is not yet understood. Using co-immunoprecipitations we report that SNX33 forms homodimers, but not heterodimers, with other BAR domain-containing proteins, such as SNX9. Domain deletion analysis revealed that the BAR domain, but not the SH3 (Src homology 3) domain, was required for homodimerization of SNX33. Additionally, the BAR domain prevented the heterodimerization between SNX9 and SNX33, as determined by domain swap experiments. Molecular modelling of the SNX33 BAR domain structure revealed that key amino acids located at the BAR domain dimer interface of the SNX9 homodimer are not conserved in SNX33. Replacing these amino acids in SNX9 with the corresponding amino acids of SNX33 allowed the mutant SNX9 to heterodimerize with SNX33. Taken together, the present study identifies critical amino acids within the BAR domains of SNX9 and SNX33 as determinants for the specificity of BAR domain-mediated interactions and suggests that SNX9 and SNX33 have distinct molecular functions.
Skip Nav Destination
Article navigation
January 2011
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 15 2010
Specific amino acids in the BAR domain allow homodimerization and prevent heterodimerization of sorting nexin 33
Bastian Dislich;
Bastian Dislich
*DZNE - German Center for Neurodegenerative Diseases, Munich, 80336 Munich, Germany
†Adolf-Butenandt-Institute, Biochemistry, Ludwig-Maximilians-University, 80336 Munich, Germany
Search for other works by this author on:
Manuel E. Than;
Manuel E. Than
‡Protein Crystallography Group, Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), 07745 Jena, Germany
Search for other works by this author on:
Stefan F. Lichtenthaler
Stefan F. Lichtenthaler
1
*DZNE - German Center for Neurodegenerative Diseases, Munich, 80336 Munich, Germany
†Adolf-Butenandt-Institute, Biochemistry, Ludwig-Maximilians-University, 80336 Munich, Germany
1To whom correspondence should be addressed (email stefan.lichtenthaler@med.uni-muenchen.de).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 13 2010
Revision Received:
October 08 2010
Accepted:
October 22 2010
Accepted Manuscript online:
October 22 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 433 (1): 75–83.
Article history
Received:
May 13 2010
Revision Received:
October 08 2010
Accepted:
October 22 2010
Accepted Manuscript online:
October 22 2010
Citation
Bastian Dislich, Manuel E. Than, Stefan F. Lichtenthaler; Specific amino acids in the BAR domain allow homodimerization and prevent heterodimerization of sorting nexin 33. Biochem J 1 January 2011; 433 (1): 75–83. doi: https://doi.org/10.1042/BJ20100709
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.