2PET

Lutheran glycoprotein, N-terminal domains 1 and 2.

2PET の概要

• エントリーDOI: 10.2210/pdb2pet/pdb
• 分子名称: Lutheran blood group glycoprotein (2 entities in total)
• 機能のキーワード: immunoglobulin superfamily., cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P50895
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25647.83

構造登録者

Burton, N.,Brady, R.L. (登録日: 2007-04-03, 公開日: 2007-12-04, 最終更新日: 2024-11-13)

主引用文献

Mankelow, T.J.,Burton, N.,Stefansdottir, F.O.,Spring, F.A.,Parsons, S.F.,Pedersen, J.S.,Oliveira, C.L.,Lammie, D.,Wess, T.,Mohandas, N.,Chasis, J.A.,Brady, R.L.,Anstee, D.J.
The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3.
Blood, 110:3398-3406, 2007

PubMed Abstract: The Lutheran blood group glycoprotein, first discovered on erythrocytes, is widely expressed in human tissues. It is a ligand for the alpha5 subunit of Laminin 511/521, an extracellular matrix protein. This interaction may contribute to vaso-occlusive events that are an important cause of morbidity in sickle cell disease. Using x-ray crystallography, small-angle x-ray scattering, and site-directed mutagenesis, we show that the extracellular region of Lutheran forms an extended structure with a distinctive bend between the second and third immunoglobulin-like domains. The linker between domains 2 and 3 appears to be flexible and is a critical determinant in maintaining an overall conformation for Lutheran that is capable of binding to Laminin. Mutagenesis studies indicate that Asp312 of Lutheran and the surrounding cluster of negatively charged residues in this linker region form the Laminin-binding site. Unusually, receptor binding is therefore not a function of the domains expected to be furthermost from the plasma membrane. These studies imply that structural flexibility of Lutheran may be essential for its interaction with Laminin and present a novel opportunity for the development of therapeutics for sickle cell disease.

PubMed: 17638854
DOI: 10.1182/blood-2007-06-094748

実験手法

X-RAY DIFFRACTION (1.7 Å)