التفاصيل البيبلوغرافية
| العنوان: |
Structure of a truncation mutant of the nuclear export factor CRM1 provides insights into the auto-inhibitory role of its C-terminal helix. |
| المؤلفون: |
Dian, Cyril, Bernaudat, Florent, Langer, Karla, Oliva, Mizar Francesca, Fornerod, Maarten, Schoehn, Guy, Müller, Christoph W, Petosa, Carlo |
| المساهمون: |
Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 )-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) |
| المصدر: |
ISSN: 1878-4186. |
| بيانات النشر: |
HAL CCSD |
| سنة النشر: |
2013 |
| المجموعة: |
HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives) |
| مصطلحات موضوعية: |
MESH: Crystallography, X-Ray, MESH: Humans, MESH: Protein Stability, MESH: Protein Structure, Secondary, MESH: Receptors, Cytoplasmic and Nuclear, MESH: Repetitive Sequences, Amino Acid, MESH: Scattering, Small Angle, MESH: Sequence Deletion, MESH: Karyopherins, MESH: Models, Molecular, MESH: Mutagenesis, MESH: Point Mutation, MESH: Protein Binding, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] |
| الوصف: |
International audience ; Chromosome region maintenance 1/exportin1/Xpo1 (CRM1) associates with the GTPase Ran to mediate the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES). CRM1 consists of helical hairpin HEAT repeats and a C-terminal helical extension (C-extension) that inhibits the binding of NES-bearing cargos. We report the crystal structure and small-angle X-ray scattering analysis of a human CRM1 mutant with enhanced NES-binding activity due to deletion of the C-extension. We show that loss of the C-extension leads to a repositioning of CRM1's C-terminal repeats and to a more extended overall conformation. Normal mode analysis predicts reduced rigidity for the deletion mutant, consistent with an observed decrease in thermal stability. Point mutations that destabilize the C-extension shift CRM1 to the more extended conformation, reduce thermal stability, and enhance NES-binding activity. These findings suggest that an important mechanism by which the C-extension regulates CRM1's cargo-binding affinity is by modulating the conformation and flexibility of its HEAT repeats. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
info:eu-repo/semantics/altIdentifier/pmid/23850454; hal-01322366; https://hal.univ-grenoble-alpes.fr/hal-01322366Test; PUBMED: 23850454 |
| الإتاحة: |
https://hal.univ-grenoble-alpes.fr/hal-01322366Test |
| رقم الانضمام: |
edsbas.A69AFFF6 |
| قاعدة البيانات: |
BASE |
