7C00

Crystal structure of the SRCR domain of human SCARA5.

7C00 の概要

• エントリーDOI: 10.2210/pdb7c00/pdb
• 分子名称: Scavenger receptor class A member 5, 2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: scara5, srcr, sr class a, scavenger receptor, ferritin, immune system
• 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: 13456.11

構造登録者

Yu, B.,He, Y. (登録日: 2020-04-29, 公開日: 2020-09-16, 最終更新日: 2024-10-23)

主引用文献

Yu, B.,Cheng, C.,Wu, Y.,Guo, L.,Kong, D.,Zhang, Z.,Wang, Y.,Zheng, E.,Liu, Y.,He, Y.
Interactions of ferritin with scavenger receptor class A members.
J.Biol.Chem., 295:15727-15741, 2020

PubMed Abstract: Scavenger receptors are a superfamily of membrane-bound receptors that recognize both self and nonself targets. Scavenger receptor class A (SR-A) has five known members (SCARA1 to -5 or SR-A1 to -A5), which are type II transmembrane proteins that form homotrimers on the cell surface. SR-A members recognize various ligands and are involved in multiple biological pathways. Among them, SCARA5 can function as a ferritin receptor; however, the interaction between SCARA5 and ferritin has not been fully characterized. Here, we determine the crystal structures of the C-terminal scavenger receptor cysteine-rich (SRCR) domain of both human and mouse SCARA5 at 1.7 and 2.5 Å resolution, respectively, revealing three Ca-binding sites on the surface. Using biochemical assays, we show that the SRCR domain of SCARA5 recognizes ferritin in a Ca-dependent manner, and both L- and H-ferritin can be recognized by SCARA5 through the SRCR domain. Furthermore, the potential binding region of SCARA5 on the surface of ferritin is explored by mutagenesis studies. We also examine the interactions of ferritin with other SR-A members and find that SCARA1 (SR-A1, CD204) and MARCO (SR-A2, SCARA2), which are highly expressed on macrophages, also interact with ferritin. By contrast, SCARA3 and SCARA4, the two SR-A members without the SRCR domain, have no detectable binding with ferritin. Overall, these results provide a mechanistic view regarding the interactions between the SR-A members and ferritin that may help to understand the regulation of ferritin homeostasis by scavenger receptors.

PubMed: 32907880
DOI: 10.1074/jbc.RA120.014690

実験手法

X-RAY DIFFRACTION (1.7 Å)