8EGX

Complex of Fat4(EC1-4) bound to Dchs1(EC1-4)

8EGX の概要

• エントリーDOI: 10.2210/pdb8egx/pdb
• 分子名称: Protocadherin Fat 4, Protocadherin-16, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: fat4, dachsous1, cadherin, protocadherin, adhesion, fat, dachsous, cell adhesion
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97771.32

構造登録者

Medina, E.,Luca, V.C. (登録日: 2022-09-13, 公開日: 2023-02-22, 最終更新日: 2024-11-20)

主引用文献

Medina, E.,Easa, Y.,Lester, D.K.,Lau, E.K.,Sprinzak, D.,Luca, V.C.
Structure of the planar cell polarity cadherins Fat4 and Dachsous1.
Nat Commun, 14:891-891, 2023

PubMed Abstract: The atypical cadherins Fat and Dachsous are key regulators of cell growth and animal development. In contrast to classical cadherins, which form homophilic interactions to segregate cells, Fat and Dachsous cadherins form heterophilic interactions to induce cell polarity within tissues. Here, we determine the co-crystal structure of the human homologs Fat4 and Dachsous1 (Dchs1) to establish the molecular basis for Fat-Dachsous interactions. The binding domains of Fat4 and Dchs1 form an extended interface along extracellular cadherin (EC) domains 1-4 of each protein. Biophysical measurements indicate that Fat4-Dchs1 affinity is among the highest reported for cadherin superfamily members, which is attributed to an extensive network of salt bridges not present in structurally similar protocadherin homodimers. Furthermore, modeling suggests that unusual extracellular phosphorylation modifications directly modulate Fat-Dachsous binding by introducing charged contacts across the interface. Collectively, our analyses reveal how the molecular architecture of Fat4-Dchs1 enables them to form long-range, high-affinity interactions to maintain planar cell polarity.

PubMed: 36797229
DOI: 10.1038/s41467-023-36435-x

実験手法

X-RAY DIFFRACTION (3.688 Å)