6ANU

Cryo-EM structure of F-actin complexed with the beta-III-spectrin actin-binding domain

6ANU の概要

• エントリーDOI: 10.2210/pdb6anu/pdb
• EMDBエントリー: 8886
• 分子名称: Actin, cytoplasmic 1, Spectrin beta chain, non-erythrocytic 2 (2 entities in total)
• 機能のキーワード: actin binding protein, filament, structural protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 447838.81

構造登録者

Wang, F.,Orlova, A.,Avery, A.W.,Hays, T.S.,Egelman, E.H. (登録日: 2017-08-14, 公開日: 2017-11-22, 最終更新日: 2024-03-13)

主引用文献

Avery, A.W.,Fealey, M.E.,Wang, F.,Orlova, A.,Thompson, A.R.,Thomas, D.D.,Hays, T.S.,Egelman, E.H.
Structural basis for high-affinity actin binding revealed by a beta-III-spectrin SCA5 missense mutation.
Nat Commun, 8:1350-1350, 2017

PubMed Abstract: Spinocerebellar ataxia type 5 (SCA5) is a neurodegenerative disease caused by mutations in the cytoskeletal protein β-III-spectrin. Previously, a SCA5 mutation resulting in a leucine-to-proline substitution (L253P) in the actin-binding domain (ABD) was shown to cause a 1000-fold increase in actin-binding affinity. However, the structural basis for this increase is unknown. Here, we report a 6.9 Å cryo-EM structure of F-actin complexed with the L253P ABD. This structure, along with co-sedimentation and pulsed-EPR measurements, demonstrates that high-affinity binding caused by the CH2-localized mutation is due to opening of the two CH domains. This enables CH1 to bind actin aided by an unstructured N-terminal region that becomes α-helical upon binding. This helix is required for association with actin as truncation eliminates binding. Collectively, these results shed light on the mechanism by which β-III-spectrin, and likely similar actin-binding proteins, interact with actin, and how this mechanism can be perturbed to cause disease.

PubMed: 29116080
DOI: 10.1038/s41467-017-01367-w

実験手法

ELECTRON MICROSCOPY (7 Å)