Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein
The T347S polymorphism in the human apolipoprotein (apo) A-IV gene is present at high frequencies among all the world's populations. Carriers of a 347S allele exhibit faster clearance of triglyceride-rich lipoproteins, greater adiposity, and increased risk for developing atherosclerosis, which...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520422965 |
| _version_ | 1818726950359793664 |
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| author | Richard B. Weinberg Victoria R. Cook |
| author_facet | Richard B. Weinberg Victoria R. Cook |
| author_sort | Richard B. Weinberg |
| collection | DOAJ |
| description | The T347S polymorphism in the human apolipoprotein (apo) A-IV gene is present at high frequencies among all the world's populations. Carriers of a 347S allele exhibit faster clearance of triglyceride-rich lipoproteins, greater adiposity, and increased risk for developing atherosclerosis, which suggests that this conservative amino acid substitution alters the structure of apo A-IV. Herein we have used spectroscopic and surface chemistry techniques to examine the structure, stability, and interfacial properties of the apo A-IV 347S isoprotein. Circular dichroism spectroscopy revealed that the 347S isoprotein has similar α-helical structure but lower thermodynamic stability than the 347T isoprotein. Fluorescence spectroscopy found that the 347S isoprotein exhibits an enhanced tyrosine emission and reduced tyrosine→tryptophan energy transfer, and second derivative UV absorption spectra noted increased tyrosine exposure, suggesting that the 347S isoprotein adopts a looser tertiary conformation. Surface chemistry studies found that although the 347S isoprotein bound rapidly to the lipid interface, it has a lower interfacial exclusion pressure and lower elastic modulus than the 347T isoprotein. Together, these observations establish that the T347S substitution alters the conformation of apo A-IV and lowers its interfacial activity—changes that could account for the effect of this polymorphism on postprandial lipid metabolism. |
| first_indexed | 2024-12-17T22:06:21Z |
| format | Article |
| id | doaj.art-05b4dcc57adc48eb831f6c57ac7d83c9 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:06:21Z |
| publishDate | 2010-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-05b4dcc57adc48eb831f6c57ac7d83c92022-12-21T21:30:51ZengElsevierJournal of Lipid Research0022-22752010-09-0151926642671Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoproteinRichard B. Weinberg0Victoria R. Cook1To whom correspondence should be addressed. weinberg@wfubmc.edu; Departments of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC; Departments of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NCDepartments of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NCThe T347S polymorphism in the human apolipoprotein (apo) A-IV gene is present at high frequencies among all the world's populations. Carriers of a 347S allele exhibit faster clearance of triglyceride-rich lipoproteins, greater adiposity, and increased risk for developing atherosclerosis, which suggests that this conservative amino acid substitution alters the structure of apo A-IV. Herein we have used spectroscopic and surface chemistry techniques to examine the structure, stability, and interfacial properties of the apo A-IV 347S isoprotein. Circular dichroism spectroscopy revealed that the 347S isoprotein has similar α-helical structure but lower thermodynamic stability than the 347T isoprotein. Fluorescence spectroscopy found that the 347S isoprotein exhibits an enhanced tyrosine emission and reduced tyrosine→tryptophan energy transfer, and second derivative UV absorption spectra noted increased tyrosine exposure, suggesting that the 347S isoprotein adopts a looser tertiary conformation. Surface chemistry studies found that although the 347S isoprotein bound rapidly to the lipid interface, it has a lower interfacial exclusion pressure and lower elastic modulus than the 347T isoprotein. Together, these observations establish that the T347S substitution alters the conformation of apo A-IV and lowers its interfacial activity—changes that could account for the effect of this polymorphism on postprandial lipid metabolism.http://www.sciencedirect.com/science/article/pii/S0022227520422965genetic polymorphismcircular dichroism spectroscopyfluorescence spectroscopyfluorescence resonance energy transferUV absorption spectroscopysurface chemistry |
| spellingShingle | Richard B. Weinberg Victoria R. Cook Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein Journal of Lipid Research genetic polymorphism circular dichroism spectroscopy fluorescence spectroscopy fluorescence resonance energy transfer UV absorption spectroscopy surface chemistry |
| title | Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein |
| title_full | Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein |
| title_fullStr | Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein |
| title_full_unstemmed | Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein |
| title_short | Distinctive structure and interfacial activity of the human apolipoprotein A-IV 347S isoprotein |
| title_sort | distinctive structure and interfacial activity of the human apolipoprotein a iv 347s isoprotein |
| topic | genetic polymorphism circular dichroism spectroscopy fluorescence spectroscopy fluorescence resonance energy transfer UV absorption spectroscopy surface chemistry |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520422965 |
| work_keys_str_mv | AT richardbweinberg distinctivestructureandinterfacialactivityofthehumanapolipoproteinaiv347sisoprotein AT victoriarcook distinctivestructureandinterfacialactivityofthehumanapolipoproteinaiv347sisoprotein |