Disparate Mutations Confer Therapeutic Gain of Hsp104 Function
نویسندگان
چکیده
منابع مشابه
Disparate Mutations Confer Therapeutic Gain of Hsp104 Function.
Hsp104, a protein disaggregase from yeast, can be engineered and potentiated to counter TDP-43, FUS, or α-synuclein misfolding and toxicity implicated in neurodegenerative disease. Here, we reveal that extraordinarily disparate mutations potentiate Hsp104. Remarkably, diverse single missense mutations at 20 different positions interspersed throughout the middle domain (MD) and small domain of n...
متن کاملDrosophila Lyra mutations are gain-of-function mutations of senseless.
The Lyra mutation was first described by Jerry Coyne in 1935. Lyra causes recessive pupal lethality and adult heterozygous Lyra mutants exhibit a dominant loss of the anterior and posterior wing margins. Unlike many mutations that cause loss of wing tissue (e.g., scalloped, Beadex, cut, and apterous-Xasta), Lyra wing discs do not exhibit increased necrotic or apoptotic cell death, nor do they s...
متن کاملGain-of-function mutations and therapeutic implications: lipoprotein lipase S447X to the rescue.
Somatic gene transfer has been extensively used to express genes of interest and probe the molecular physiology of lipoprotein metabolism and many other processes in animal models.1 Among its advantages over germ-line transgenic animals are the ability to rapidly express genes on selected genetic backgrounds without time-intensive backcrossing, the greater ability to control expression level th...
متن کاملALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and dysregulate its function, including loss of Gems and altered levels of small nuclear RNAs. The s...
متن کاملComparative Analysis of the Structure and Function of AAA+ Motors ClpA, ClpB, and Hsp104: Common Threads and Disparate Functions
Cellular proteostasis involves not only the expression of proteins in response to environmental needs, but also the timely repair or removal of damaged or unneeded proteins. AAA+ motor proteins are critically involved in these pathways. Here, we review the structure and function of AAA+ proteins ClpA, ClpB, and Hsp104. ClpB and Hsp104 rescue damaged proteins from toxic aggregates and do not par...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: ACS Chemical Biology
سال: 2015
ISSN: 1554-8929,1554-8937
DOI: 10.1021/acschembio.5b00765