| Structural highlights
Function
MFGM_MOUSE Contributes to phagocytic removal of apoptotic cells in many tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell surfaces in a receptor-independent manner. Zona pellucida-binding protein which may play a role in gamete interaction (By similarity). Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization.[1] [2]
Publication Abstract from PubMed
MFG-E8 (also known as lactadherin), which is a secreted glycoprotein from a variety of cell types, possesses two EGF domains and tandem C domains with sequence homology to that of blood coagulation proteins factor V and factor VIII. MFG-E8 binds to phosphatidylserine (PS) in membranes with high affinity. We have recently shown that the C2 domain of MFG-E8 bears more specificity toward PS when compared with phosphatidylcholine (PC), another phospholipid thought to be involved in the immune function of phagocytes. In our current study, we have determined the solution structure of the C2 domain by nuclear magnetic resonance (NMR) spectroscopy, and characterized the molecular basis of binding between the C2 domain and PS by (31)P-NMR spectroscopy. Furthermore, we also verified that that positively charged and aromatic residues clustered in loops 1-3 of the C2 domain play key roles in recognizing PS in apoptotic cells.
NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine.,Ye H, Li B, Subramanian V, Choi BH, Liang Y, Harikishore A, Chakraborty G, Baek K, Yoon HS Biochim Biophys Acta. 2013 Mar;1828(3):1083-93. doi:, 10.1016/j.bbamem.2012.12.009. Epub 2012 Dec 21. PMID:23262193[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Silvestre JS, Thery C, Hamard G, Boddaert J, Aguilar B, Delcayre A, Houbron C, Tamarat R, Blanc-Brude O, Heeneman S, Clergue M, Duriez M, Merval R, Levy B, Tedgui A, Amigorena S, Mallat Z. Lactadherin promotes VEGF-dependent neovascularization. Nat Med. 2005 May;11(5):499-506. Epub 2005 Apr 17. PMID:15834428 doi:http://dx.doi.org/10.1038/nm1233
- ↑ Bu HF, Zuo XL, Wang X, Ensslin MA, Koti V, Hsueh W, Raymond AS, Shur BD, Tan XD. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest. 2007 Dec;117(12):3673-83. PMID:18008006 doi:http://dx.doi.org/10.1172/JCI31841
- ↑ Ye H, Li B, Subramanian V, Choi BH, Liang Y, Harikishore A, Chakraborty G, Baek K, Yoon HS. NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine. Biochim Biophys Acta. 2013 Mar;1828(3):1083-93. doi:, 10.1016/j.bbamem.2012.12.009. Epub 2012 Dec 21. PMID:23262193 doi:http://dx.doi.org/10.1016/j.bbamem.2012.12.009
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