7RX0

Complex of AMPPNP-Kif7 and Gli2 Zinc-Finger domain bound to microtubules

7RX0 の概要

• エントリーDOI: 10.2210/pdb7rx0/pdb
• EMDBエントリー: 24721
• 分子名称: Kinesin-like protein KIF7, Zinc finger protein GLI2, Tubulin alpha-1A chain, ... (8 entities in total)
• 機能のキーワード: kinesin, microtubule, transcription factor, motor domain, motor protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 168977.49

構造登録者

Mani, N.,Wilson-Kubalek, E.M.,Haque, F.,Freniere, C.,Milligan, R.A.,Subramanian, R. (登録日: 2021-08-20, 公開日: 2022-06-15, 最終更新日: 2024-06-05)

主引用文献

Haque, F.,Freniere, C.,Ye, Q.,Mani, N.,Wilson-Kubalek, E.M.,Ku, P.I.,Milligan, R.A.,Subramanian, R.
Cytoskeletal regulation of a transcription factor by DNA mimicry via coiled-coil interactions.
Nat.Cell Biol., 24:1088-1098, 2022

PubMed Abstract: A long-established strategy for transcription regulation is the tethering of transcription factors to cellular membranes. By contrast, the principal effectors of Hedgehog signalling, the GLI transcription factors, are regulated by microtubules in the primary cilium and the cytoplasm. How GLI is tethered to microtubules remains unclear. Here, we uncover DNA mimicry by the ciliary kinesin KIF7 as a mechanism for the recruitment of GLI to microtubules, wherein the coiled-coil dimerization domain of KIF7, characterized by its striking shape, size and charge similarity to DNA, forms a complex with the DNA-binding zinc fingers in GLI, thus revealing a mode of tethering a DNA-binding protein to the cytoskeleton. GLI increases KIF7 microtubule affinity and consequently modulates the localization of both proteins to microtubules and the cilium tip. Thus, the kinesin-microtubule system is not a passive GLI tether but a regulatable platform tuned by the kinesin-transcription factor interaction. We retooled this coiled-coil-based GLI-KIF7 interaction to inhibit the nuclear and cilium localization of GLI. This strategy can potentially be exploited to downregulate erroneously activated GLI in human cancers.

PubMed: 35725768
DOI: 10.1038/s41556-022-00935-7

実験手法

ELECTRON MICROSCOPY (3.89 Å)