6OFP

Structure of the C-terminal cargo binding domain of human Bicaudal D2

6OFP の概要

• エントリーDOI: 10.2210/pdb6ofp/pdb
• 分子名称: Protein bicaudal D homolog 2 (2 entities in total)
• 機能のキーワード: bicaudal d2, dynein, dynein adaptor, coiled-coil, registry shift, spinal muscular atrophy, cytoskeletal motor, motor protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21875.16

構造登録者

Noell, C.R.,Debler, E.W.,Cui, H.,Solmaz, S.R. (登録日: 2019-03-31, 公開日: 2019-07-24, 最終更新日: 2023-10-11)

主引用文献

Noell, C.R.,Loh, J.Y.,Debler, E.W.,Loftus, K.M.,Cui, H.,Russ, B.B.,Zhang, K.,Goyal, P.,Solmaz, S.R.
Role of Coiled-Coil Registry Shifts in the Activation of Human Bicaudal D2 for Dynein Recruitment upon Cargo Binding.
J Phys Chem Lett, 10:4362-4367, 2019

PubMed Abstract: Dynein adaptors such as Bicaudal D2 (BicD2) recognize cargo for dynein-dependent transport, and cargo-bound adaptors are required to activate dynein for processive transport, but the mechanism of action is unknown. Here we report the X-ray structure of the cargo-binding domain of human BicD2 and investigate the structural dynamics of the coiled-coil. Our molecular dynamics simulations support the fact that BicD2 can switch from a homotypic coiled-coil registry, in which both helices of the homodimer are aligned, to an asymmetric registry, where a portion of one helix is vertically shifted, as both states are similarly stable and defined by distinct conformations of F743. The F743I variant increases dynein recruitment in the homologue, whereas the human R747C variant causes spinal muscular atrophy. We report spontaneous registry shifts for both variants, which may be the cause for BicD2 hyperactivation and disease. We propose that a registry shift upon cargo binding may activate autoinhibited BicD2 for dynein recruitment.

PubMed: 31306018
DOI: 10.1021/acs.jpclett.9b01865

実験手法

X-RAY DIFFRACTION (2.006 Å)