Type C mutation of nucleophosmin 1 acute myeloid leukemia: Consequences of intrinsic disorder.
Abstrak
BACKGROUND Nucleophosmin 1 (NPM1) protein is a multifunctional nucleolar chaperone and its gene is the most frequently mutated in Acute Myeloid Leukemia (AML). AML mutations cause the unfolding of the C-terminal domain (CTD) and the protein delocalizing in the cytosol (NPM1c+). Marked aggregation endowed with an amyloid character was assessed as consequences of mutations. SCOPE Herein we analyzed the effects of type C mutation on two protein regions: i) a N-terminal extended version of the CTD, named Cterm_mutC and ii) a shorter polypeptide including the sequences of the second and third helices of the CTD, named H2_mutC. MAJOR CONCLUSIONS Both demonstrated able to self-assembly with different kinetics and conformational intermediates and to provide fibers presenting large flexible regions. GENERAL SIGNIFICANCE The present study adds a new piece of knowledge to the effects of AML-mutations on structural biology of Nucleophosmin 1, that could be exploited in therapeutic interventions targeting selectively NPMc+.
Topik & Kata Kunci
Penulis (7)
S. La Manna
Daniele Florio
Concetta Di Natale
E. Lagreca
T. Sibillano
C. Giannini
D. Marasco
Akses Cepat
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Cek di sumber asli →- Tahun Terbit
- 2022
- Bahasa
- en
- Total Sitasi
- 8×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1016/j.bbagen.2022.130173
- Akses
- Open Access ✓