Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026838 (
spasticity
)
6,471
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations of human spastin, an AAA (ATPases associated with diverse cellular activity) family protein, cause an autosomal dominant form of hereditary spastic paraplegia, which is characterized by weakness,
spasticity
and loss of the vibratory sense in the lower limbs. Recently, it has been reported that spastin displays microtubule-severing activity. We also previously reported that Caenorhabditis elegans spastin homologue
SPAS-1
displays microtubule severing. However, the detailed molecular mechanism of microtubule severing remains unknown. Here, we describe that
SPAS-1
forms a stable hexamer in a concentration-dependent manner and that ATPase activity of
SPAS-1
is greatly stimulated by microtubules. Furthermore, MTBD (microtubule-binding domain) of
SPAS-1
is essential for binding to microtubules. Taken these results together, we propose that MTBD of
SPAS-1
plays a critical role in enrichment of
SPAS-1
to microtubules, where
SPAS-1
is concentrated and able to form a stable hexamer, subsequently its ATPase activity is stimulated. On the other hand, our mutational analyses revealed that the conserved aromatic and basic amino acid residues in the pore region are important for microtubule severing. We also detected the direct interaction of the extremely acidic C-terminal polypeptide of tubulin with
SPAS-1
. Consequently, we propose that the central pore residues are important for the recognition of substrates.
...
PMID:Conserved aromatic and basic amino acid residues in the pore region of Caenorhabditis elegans spastin play critical roles in microtubule severing. 1961 44
