| Structural highlights
Function
[TIMD4_MOUSE] Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Involved in regulating T-cell proliferation and lymphotoxin signaling. Ligand for HAVCR1/TIMD1.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The T cell immunoglobulin and mucin domain (TIM) proteins are important regulators of T cell responses. Crystal structures of the murine TIM-4 identified a metal-ion-dependent ligand binding site (MILIBS) in the immunoglobulin (Ig) domain of the TIM family. The characteristic CC' loop of the TIM domain and the hydrophobic FG loop shaped a narrow cavity where acidic compounds penetrate and coordinate to a metal ion bound to conserved residues in the TIM proteins. The structure of phosphatidylserine bound to the Ig domain showed that the hydrophilic head penetrates into the MILIBS and coordinates with the metal ion, whereas the aromatic residues on the tip of the FG loop interacted with the fatty acid chains and could insert into the lipid bilayer. Our results also revealed an important role of the MILIBS in the trafficking of TIM-1 to the cell surface.
Structures of T cell immunoglobulin mucin protein 4 show a metal-Ion-dependent ligand binding site where phosphatidylserine binds.,Santiago C, Ballesteros A, Martinez-Munoz L, Mellado M, Kaplan GG, Freeman GJ, Casasnovas JM Immunity. 2007 Dec;27(6):941-51. PMID:18083575[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shakhov AN, Rybtsov S, Tumanov AV, Shulenin S, Dean M, Kuprash DV, Nedospasov SA. SMUCKLER/TIM4 is a distinct member of TIM family expressed by stromal cells of secondary lymphoid tissues and associated with lymphotoxin signaling. Eur J Immunol. 2004 Feb;34(2):494-503. PMID:14768054 doi:http://dx.doi.org/10.1002/eji.200324590
- ↑ Meyers JH, Chakravarti S, Schlesinger D, Illes Z, Waldner H, Umetsu SE, Kenny J, Zheng XX, Umetsu DT, DeKruyff RH, Strom TB, Kuchroo VK. TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation. Nat Immunol. 2005 May;6(5):455-64. Epub 2005 Mar 27. PMID:15793576 doi:http://dx.doi.org/10.1038/ni1185
- ↑ Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature. 2007 Nov 15;450(7168):435-9. Epub 2007 Oct 24. PMID:17960135 doi:http://dx.doi.org/10.1038/nature06307
- ↑ Santiago C, Ballesteros A, Martinez-Munoz L, Mellado M, Kaplan GG, Freeman GJ, Casasnovas JM. Structures of T cell immunoglobulin mucin protein 4 show a metal-Ion-dependent ligand binding site where phosphatidylserine binds. Immunity. 2007 Dec;27(6):941-51. PMID:18083575 doi:http://dx.doi.org/10.1016/j.immuni.2007.11.008
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