3KAA

Structure of Tim-3 in complex with phosphatidylserine

3KAA の概要

• エントリーDOI: 10.2210/pdb3kaa/pdb
• 分子名称: Hepatitis A virus cellular receptor 2, CALCIUM ION, 1,2-DICAPROYL-SN-PHOSPHATIDYL-L-SERINE, ... (4 entities in total)
• 機能のキーワード: ig-like, protein-ligand complex, beta barrel, receptor, immune system
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27208.40

構造登録者

Ballesteros, A.,Santiago, C.,Casasnovas, J.M. (登録日: 2009-10-19, 公開日: 2010-01-26, 最終更新日: 2024-10-16)

主引用文献

DeKruyff, R.H.,Bu, X.,Ballesteros, A.,Santiago, C.,Chim, Y.L.,Lee, H.H.,Karisola, P.,Pichavant, M.,Kaplan, G.G.,Umetsu, D.T.,Freeman, G.J.,Casasnovas, J.M.
T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells.
J.Immunol., 184:1918-1930, 2010

PubMed Abstract: T cell/transmembrane, Ig, and mucin (TIM) proteins, identified using a congenic mouse model of asthma, critically regulate innate and adaptive immunity. TIM-1 and TIM-4 are receptors for phosphatidylserine (PtdSer), exposed on the surfaces of apoptotic cells. Herein, we show with structural and biological studies that TIM-3 is also a receptor for PtdSer that binds in a pocket on the N-terminal IgV domain in coordination with a calcium ion. The TIM-3/PtdSer structure is similar to that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TIM family members. Fibroblastic cells expressing mouse or human TIM-3 bound and phagocytosed apoptotic cells, with the BALB/c allelic variant of mouse TIM-3 showing a higher capacity than the congenic C.D2 Es-Hba-allelic variant. These functional differences were due to structural differences in the BC loop of the IgV domain of the TIM-3 polymorphic variants. In contrast to fibroblastic cells, T or B cells expressing TIM-3 formed conjugates with but failed to engulf apoptotic cells. Together these findings indicate that TIM-3-expressing cells can respond to apoptotic cells, but the consequence of TIM-3 engagement of PtdSer depends on the polymorphic variants of and type of cell expressing TIM-3. These findings establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene family, which has been associated with asthma and autoimmunity and shown to modulate peripheral tolerance.

PubMed: 20083673
DOI: 10.4049/jimmunol.0903059

実験手法

X-RAY DIFFRACTION (3.002 Å)