Self assembly of human septin 2 into amyloid filaments

Julio Cesar Pissuti Damalio, Wanius Garcia, Joci Neuby Alves MacÊdo, Ivo De Almeida Marques, José M. Andreu, Rafael Giraldo, Richard Charles Garratt, Ana Paula Ulian Araújo

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)628-636
Number of pages9
Issue number3
StatePublished - Mar 2012
Externally publishedYes


  • Aggregates
  • Amyloid
  • GTPase domain
  • Neurodegenerative diseases
  • Septin

ASJC Scopus subject areas

  • Biochemistry


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