TY - JOUR
T1 - Self assembly of human septin 2 into amyloid filaments
AU - Pissuti Damalio, Julio Cesar
AU - Garcia, Wanius
AU - Alves MacÊdo, Joci Neuby
AU - De Almeida Marques, Ivo
AU - Andreu, José M.
AU - Giraldo, Rafael
AU - Garratt, Richard Charles
AU - Ulian Araújo, Ana Paula
PY - 2012/3
Y1 - 2012/3
N2 - Septins are a conserved group of GTP-binding proteins that form hetero-oligomeric complexes which assemble into filaments. These are essential for septin function, including their role in cytokinesis, cell division, exocytosis and membrane trafficking. Septin 2 (SEPT2) is a member of the septin family and has been associated with neurofibrillary tangles and other pathological features of senile plaques in Alzheimer's disease. An in silico analysis of the amino acid sequence of SEPT2 identified regions with a significant tendency to aggregate and/or form amyloid. These were all observed within the GTP-binding domain. This was consistent with the experimental identification of a structure rich in β-sheet during temperature induced unfolding transitions observed for both the full length protein and the GTP-binding domain alone. This intermediate state is characterized by irreversible aggregation and has the ability to bind Thioflavin-T, suggesting its amyloid nature. Under electron microscopy, fibers extending for several micrometers in length could be visualized. The results shown in this study support the hypothesis that single septins, when present in excess or with unbalanced stoichiometries, may be unstable and assemble into amyloid-like structures.
AB - Septins are a conserved group of GTP-binding proteins that form hetero-oligomeric complexes which assemble into filaments. These are essential for septin function, including their role in cytokinesis, cell division, exocytosis and membrane trafficking. Septin 2 (SEPT2) is a member of the septin family and has been associated with neurofibrillary tangles and other pathological features of senile plaques in Alzheimer's disease. An in silico analysis of the amino acid sequence of SEPT2 identified regions with a significant tendency to aggregate and/or form amyloid. These were all observed within the GTP-binding domain. This was consistent with the experimental identification of a structure rich in β-sheet during temperature induced unfolding transitions observed for both the full length protein and the GTP-binding domain alone. This intermediate state is characterized by irreversible aggregation and has the ability to bind Thioflavin-T, suggesting its amyloid nature. Under electron microscopy, fibers extending for several micrometers in length could be visualized. The results shown in this study support the hypothesis that single septins, when present in excess or with unbalanced stoichiometries, may be unstable and assemble into amyloid-like structures.
KW - Aggregates
KW - Amyloid
KW - GTPase domain
KW - Neurodegenerative diseases
KW - Septin
UR - http://www.scopus.com/inward/record.url?scp=84857059876&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857059876&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2011.09.014
DO - 10.1016/j.biochi.2011.09.014
M3 - Article
C2 - 21967827
AN - SCOPUS:84857059876
SN - 0300-9084
VL - 94
SP - 628
EP - 636
JO - Biochimie
JF - Biochimie
IS - 3
ER -