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Insights into the oligomerization of CRMP s: crystal structure of human collapsin response mediator protein 5
Author(s) -
Ponnusamy Rajesh,
Lohkamp Bernhard
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12188
Subject(s) - mediator , microbiology and biotechnology , phosphoprotein , oligomer , tetramer , cytosol , cytoskeleton , chemistry , biology , biochemistry , phosphorylation , enzyme , cell , organic chemistry
Collapsin response mediator protein‐5 ( CRMP ‐5) is the latest identified member of the CRMP cytosolic phosphoprotein family, which is crucial for neuronal development and repair. CRMP s exist as homo‐ and/or hetero‐tetramers in vivo and participate in signaling transduction, cytoskeleton rearrangements, and endocytosis. CRMP ‐5 antagonizes many of the other CRMP s' functions either by directly interacting with them or by competing for their binding partners. We determined the crystal structures of a full length and a truncated version of human CRMP ‐5, both of which form a homo‐tetramer similar to those observed in CRMP ‐1 and CRMP ‐2. However, solution studies indicate that CRMP ‐5 and CRMP ‐1 form weaker homo‐tetramers compared with CRMP ‐2, and that divalent cations, Ca 2+ and Mg 2+ , destabilize oligomers of CRMP ‐5 and CRMP ‐1, but promote CRMP ‐2 oligomerization. On the basis of comparative analysis of the CRMP ‐5 crystal structure, we identified residues that are crucial for determining the preference for hetero‐oligomer or homo‐oligomer formation. We also show that in spite of being the CRMP family member most closely related to dihydropyrimidinase, CRMP ‐5 does not have any detectable amidohydrolase activity. The presented findings provide new detailed insights into the structure, oligomerization, and regulation of CRMP s.