6TPT

Crystal structures of FNIII domain three and four of the human leucocyte common antigen-related protein, LAR

6TPT の概要

• エントリーDOI: 10.2210/pdb6tpt/pdb
• 分子名称: Receptor-type tyrosine-protein phosphatase F (1 entity in total)
• 機能のキーワード: fibronectin type-iii, adhesion protein, cell adhesion
• 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: 21902.21

構造登録者

Vilstrup, J.P.,Thirup, S.S.,Simonsen, A.,Birkefeldt, T.,Strandbygaard, D. (登録日: 2019-12-14, 公開日: 2020-05-13, 最終更新日: 2024-01-24)

主引用文献

Vilstrup, J.,Simonsen, A.,Birkefeldt, T.,Strandbygard, D.,Lyngso, J.,Pedersen, J.S.,Thirup, S.
Crystal and solution structures of fragments of the human leucocyte common antigen-related protein.
Acta Crystallogr D Struct Biol, 76:406-417, 2020

PubMed Abstract: Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LAR) showed a characteristic L shape. SAXS data suggested limited flexibility within LAR, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LAR) and the four C-terminal FNIII domains (LAR) both bound heparin, while LAR did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LAR and LAR, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR.

PubMed: 32355037
DOI: 10.1107/S2059798320003885

実験手法

X-RAY DIFFRACTION (3.2 Å)