2X2U

First two Cadherin-like domains from Human RET

Summary for 2X2U

• Entry DOI: 10.2210/pdb2x2u/pdb
• Related: 1XPD 2IVS 2IVT 2IVU 2IVV 2X2K 2X2L 2X2M
• Descriptor: 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)
• Functional Keywords: hirschsprung disease, extracellular domain, disease mutation, transferase, glycoprotein, transmembrane, kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 30071.62

Authors

Kjaer, S.,Hanrahan, S.,Purkiss-Trew, A.G.,Totty, N.,McDonald, N.Q. (deposition date: 2010-01-15, release date: 2010-05-19, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)