2X2U

First two Cadherin-like domains from Human RET

2X2U の概要

• エントリーDOI: 10.2210/pdb2x2u/pdb
• 関連するPDBエントリー: 1XPD 2IVS 2IVT 2IVU 2IVV 2X2K 2X2L 2X2M
• 分子名称: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, UNKNOWN ATOM OR ION, ... (6 entities in total)
• 機能のキーワード: hirschsprung disease, extracellular domain, disease mutation, transferase, glycoprotein, transmembrane, kinase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30071.62

構造登録者

Kjaer, S.,Hanrahan, S.,Purkiss-Trew, A.G.,Totty, N.,McDonald, N.Q. (登録日: 2010-01-15, 公開日: 2010-05-19, 最終更新日: 2024-10-23)

主引用文献

Kjaer, S.,Hanrahan, S.,Totty, N.,McDonald, N.Q.
Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations.
Nat. Struct. Mol. Biol., 17:726-731, 2010

PubMed Abstract: The maturation of human RET is adversely affected by a range of missense mutations found in patients with Hirschsprung's disease (HSCR), a complex multigenic disease. Here we show that two N-terminal cadherin-like domains, CLD1 and CLD2 (CLD(1-2)), from human RET adopt a clam-shell arrangement distinct from that of classical cadherins. CLD1 structural elements and disulfide composition are unique to mammals, indicating an unexpected structural diversity within higher and lower vertebrate RET CLD regions. We identify two unpaired cysteines that predispose human RET to maturation impediments in the endoplasmic reticulum and establish a quantitative cell-based RET maturation assay that offers a biochemical correlate of HSCR disease severity. Our findings provide a key conceptual framework and means of testing and predicting genotype-phenotype correlations in HSCR.

PubMed: 20473317
DOI: 10.1038/nsmb.1808

実験手法

X-RAY DIFFRACTION (2 Å)