5UV6

Crystal structure of human Opioid Binding Protein/Cell Adhesion Molecule Like (OPCML)

5UV6 の概要

• エントリーDOI: 10.2210/pdb5uv6/pdb
• 分子名称: Opioid-binding protein/cell adhesion molecule, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: gpi-anchored ig domain cell 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: 65309.34

構造登録者

Birtley, J.R.,Stern, L.J.,Gabra, H.,Zanini, E. (登録日: 2017-02-19, 公開日: 2018-03-21, 最終更新日: 2024-11-06)

主引用文献

Birtley, J.R.,Alomary, M.,Zanini, E.,Antony, J.,Maben, Z.,Weaver, G.C.,Von Arx, C.,Mura, M.,Marinho, A.T.,Lu, H.,Morecroft, E.V.N.,Karali, E.,Chayen, N.E.,Tate, E.W.,Jurewicz, M.,Stern, L.J.,Recchi, C.,Gabra, H.
Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions.
Nat Commun, 10:3134-3134, 2019

PubMed Abstract: OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers.

PubMed: 31316070
DOI: 10.1038/s41467-019-10966-8

実験手法

X-RAY DIFFRACTION (2.65001977608 Å)