7KBU

Structure of Hevin FS-EC

7KBU の概要

• エントリーDOI: 10.2210/pdb7kbu/pdb
• 分子名称: Proliferation-inducing protein 33, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (7 entities in total)
• 機能のキーワード: hevin, sparc, neurexins, neuroligins, mdgas, synaptic organizer, adhesion molecule, cell adhesion
• 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: 58545.57

構造登録者

Machius, M.,Fan, S.,Rudenko, G. (登録日: 2020-10-03, 公開日: 2021-02-10, 最終更新日: 2024-11-06)

主引用文献

Fan, S.,Gangwar, S.P.,Machius, M.,Rudenko, G.
Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges.
Structure, 29:664-, 2021

PubMed Abstract: Hevin is secreted by astrocytes and its synaptogenic effects are antagonized by the related protein, SPARC. Hevin stabilizes neurexin-neuroligin transsynaptic bridges in vivo. A third protein, membrane-tethered MDGA, blocks these bridges. Here, we reveal the molecular underpinnings of a regulatory network formed by this trio of proteins. The hevin FS-EC structure differs from SPARC, in that the EC domain appears rearranged around a conserved core. The FS domain is structurally conserved and it houses nanomolar affinity binding sites for neurexin and neuroligin. SPARC also binds neurexin and neuroligin, competing with hevin, so its antagonist action is rooted in its shortened N-terminal region. Strikingly, the hevin FS domain competes with MDGA for an overlapping binding site on neuroligin, while the hevin EC domain binds the extracellular matrix protein collagen (like SPARC), so that this trio of proteins can regulate neurexin-neuroligin transsynaptic bridges and also extracellular matrix interactions, impacting synapse formation and ultimately neural circuits.

PubMed: 33535026
DOI: 10.1016/j.str.2021.01.003

実験手法

X-RAY DIFFRACTION (2.27 Å)