Title : Crystal structure and role of glycans and
dimerization in folding of neuronal
leucine-rich repeat protein AMIGO-1
Abstract :
- AMIGO-1 is the parent member of a novel family of three cell surface leucine-rich repeat (LRR) proteins
- Its expression is induced by the binding of HMGB1 ( high-mobility group box 1 protein ) to RAGE ( receptor for advanced glycation end products ) on neurons
- Binding of HMGB1 to RAGE is known to have a direct effect on cellular growth regulation and mobility, and AMIGO-1 directly supports growth of neuronal processes and fasciculation of neurites
- In addition, the second member of the AMIGO-family, AMIGO-2 , has been implicated in adhesion of tumor cells in adenocarcinoma and survival of neurons
- We have determined the crystal structure of AMIGO-1 at 2.0 Å resolution, which reveals a typical cell surface LRR domain arrangement with N- and C-terminal capping domains with disulfide bridges, followed by a C2-type Ig domain
- AMIGO-1 is a dimer, with the LRR regions forming the dimer interface, and sequence conservation analysis and static light-scattering measurements suggest that all three AMIGO family proteins form similar dimers
- Based on the AMIGO-1 structure, we have also modeled AMIGO-2 and present small-angle X-ray scattering data on AMIGO-2 and AMIGO-3
- Our mutagenesis studies show that AMIGO-1 dimerization is necessary for proper cell surface expression and thus probably for proper or stable folding in the endoplastic reticulum and for the function of the protein
- Based on the data presented earlier, we also suggest that dimerization through the LRR-LRR interface is likely to be involved in cell-cell adhesion by AMIGO-1 , while extensive glycosylation may have a role
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. leucine-rich, , -, neuronal leucine-rich repeat protein AMIGO-1, leucine
- 1. leucine-rich, , -, three cell surface leucine-rich repeat (LRR) proteins, leucine
- 7. data, , AMIGO-2, data, -
- 7. data, , AMIGO-3, data, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):