title: NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine.
abstract: 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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Baihong
authors.initials: B
authors.lastname: Li
authors.forename: Vivekanandan
authors.initials: V
authors.lastname: Subramanian
authors.forename: Bo-Hwa
authors.initials: BH
authors.lastname: Choi
authors.forename: Yu
authors.initials: Y
authors.lastname: Liang
authors.forename: Amaravadhi
authors.initials: A
authors.lastname: Harikishore
authors.forename: Goutam
authors.initials: G
authors.lastname: Chakraborty
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Baek
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry*; D017209:Apoptosis; D001777:Blood Coagulation; D006023:Glycoproteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007107:Immune System; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008894:Milk Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000954:Antigens, Surface; D006023:Glycoproteins; C098942:MFGE8 protein, human; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D011994:Recombinant Proteins