6IAA

hRobo2 ectodomain

6IAA の概要

• エントリーDOI: 10.2210/pdb6iaa/pdb
• 関連するPDBエントリー: 6I9S
• 分子名称: Roundabout homolog 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: slit, robo, axon guidance, cell surface receptor, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 291925.37

構造登録者

Barak, R.,Isupov, N.M.,Opatowsky, Y. (登録日: 2018-11-26, 公開日: 2019-03-13, 最終更新日: 2024-10-16)

主引用文献

Barak, R.,Yom-Tov, G.,Guez-Haddad, J.,Gasri-Plotnitsky, L.,Maimon, R.,Cohen-Berkman, M.,McCarthy, A.A.,Perlson, E.,Henis-Korenblit, S.,Isupov, M.N.,Opatowsky, Y.
Structural Principles in Robo Activation and Auto-inhibition.
Cell, 177:272-285.e16, 2019

PubMed Abstract: Proper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos' switch from "off" to "on" states remains unclear. Here, we report a 3.6 Å crystal structure of the intact human Robo2 ectodomain (domains D1-8). We demonstrate that Robo cis dimerization via D4 is conserved through hRobo1, 2, and 3 and the C. elegans homolog SAX-3 and is essential for SAX-3 function in vivo. The structure reveals two levels of auto-inhibition that prevent premature activation: (1) cis blocking of the D4 dimerization interface and (2) trans interactions between opposing Robo receptors that fasten the D4-blocked conformation. Complementary experiments in mouse primary neurons and C. elegans support the auto-inhibition model. These results suggest that Slit stimulation primarily drives the release of Robo auto-inhibition required for dimerization and activation.

PubMed: 30853216
DOI: 10.1016/j.cell.2019.02.004

実験手法

X-RAY DIFFRACTION (3.6 Å)