4ZRQ

E88 deletion mutant of CD320 in complex with TC2

4ZRQ の概要

• エントリーDOI: 10.2210/pdb4zrq/pdb
• 関連するPDBエントリー: 4ZRP
• 分子名称: Transcobalamin-2, CD320 antigen, CYANOCOBALAMIN, ... (6 entities in total)
• 機能のキーワード: ldlr-r, vitamin transporter, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 119886.79

構造登録者

Alam, A.,Locher, K.P. (登録日: 2015-05-12, 公開日: 2016-07-20, 最終更新日: 2024-10-09)

主引用文献

Alam, A.,Woo, J.S.,Schmitz, J.,Prinz, B.,Root, K.,Chen, F.,Bloch, J.S.,Zenobi, R.,Locher, K.P.
Structural basis of transcobalamin recognition by human CD320 receptor.
Nat Commun, 7:12100-12100, 2016

PubMed Abstract: Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320ΔE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320ΔE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway.

PubMed: 27411955
DOI: 10.1038/ncomms12100

実験手法

X-RAY DIFFRACTION (2.6 Å)