NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine

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 affi...

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Main Author: Li, Baihong
Other Authors: Yoon Ho Sup
Format: Theses and Dissertations
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/54855
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-548552023-02-28T18:40:03Z NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine Li, Baihong Yoon Ho Sup School of Biological Sciences DRNTU::Science::Biological sciences 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 phophatidylcholine (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, characterized the molecular basis of binding between the C2 domain and PS by 31P-NMR spectroscopy. Furthermore, we also verified that positively charged and aromatic residues clustered in loops 1-3 of the C2 domain play key roles in recognizing PS in apoptotic cells. Last but not least, the influence of C1 domain on PS binding was also tested in our new Co-culture FACS analysis and confirmed its role in the binding event. DOCTOR OF PHILOSOPHY (SBS) 2013-09-30T06:39:55Z 2013-09-30T06:39:55Z 2013 2013 Thesis Li,B. (2013). NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine.. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/54855 10.32657/10356/54855 en 139 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Li, Baihong
NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine
description 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 phophatidylcholine (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, characterized the molecular basis of binding between the C2 domain and PS by 31P-NMR spectroscopy. Furthermore, we also verified that positively charged and aromatic residues clustered in loops 1-3 of the C2 domain play key roles in recognizing PS in apoptotic cells. Last but not least, the influence of C1 domain on PS binding was also tested in our new Co-culture FACS analysis and confirmed its role in the binding event.
author2 Yoon Ho Sup
author_facet Yoon Ho Sup
Li, Baihong
format Theses and Dissertations
author Li, Baihong
author_sort Li, Baihong
title NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine
title_short NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine
title_full NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine
title_fullStr NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine
title_full_unstemmed NMR solution structure of C2 domain of MFG-E8 and insights into its recognition with phosphatidylserine
title_sort nmr solution structure of c2 domain of mfg-e8 and insights into its recognition with phosphatidylserine
publishDate 2013
url https://hdl.handle.net/10356/54855
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