Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI
Scavenger receptor class B, type I (SR-BI), is a high-density lipoprotein (HDL) receptor, which also binds low-density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a coreceptor for hepatitis C virus and a signaling receptor that...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/86058 https://orcid.org/0000-0003-4541-5181 https://orcid.org/0000-0003-2673-1672 |
| _version_ | 1826214558381899776 |
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| author | Xu, Shangzhe Krieger, Monty Nieland, Thomas J. Penman, Marsha L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Xu, Shangzhe Krieger, Monty Nieland, Thomas J. Penman, Marsha L. |
| author_sort | Xu, Shangzhe |
| collection | MIT |
| description | Scavenger receptor class B, type I (SR-BI), is a high-density lipoprotein (HDL) receptor, which also binds low-density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a coreceptor for hepatitis C virus and a signaling receptor that regulates cell metabolism. Many investigators have reported that lipoproteins bind to SR-BI via a single class of independent (not interacting), high-affinity binding sites (one site model). We have reinvestigated the ligand concentration dependence of [superscript 125]I-HDL binding to SR-BI and SR-BI-mediated specific uptake of [[superscript 3]H]CE from [[superscript 3]H]CE-HDL using an expanded range of ligand concentrations (<1 μg of protein/mL, lower than previously reported). Scatchard and nonlinear least-squares model fitting analyses of the binding and uptake data were both inconsistent with a single class of independent binding sites binding univalent lipoprotein ligands. The data are best fit by models in which SR-BI has either two independent classes of binding sites or one class of sites exhibiting negative cooperativity due to either classic allostery or ensemble effects (“lattice model”). Similar results were observed for LDL. Application of the “infinite dilution” dissociation rate method established that the binding of [superscript 125]I-HDL to SR-BI at 4 °C exhibits negative cooperativity. The unexpected complexity of the interactions of lipoproteins with SR-BI should be taken into account when interpreting the results of experiments that explore the mechanism(s) by which SR-BI mediates ligand binding, lipid transport, and cell signaling. |
| first_indexed | 2024-09-23T16:07:41Z |
| format | Article |
| id | mit-1721.1/86058 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:07:41Z |
| publishDate | 2014 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/860582024-06-26T00:27:38Z Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI Xu, Shangzhe Krieger, Monty Nieland, Thomas J. Penman, Marsha L. Massachusetts Institute of Technology. Department of Biology Krieger, Monty Nieland, Thomas J. Penman, Marsha L. Krieger, Monty Xu, Shangzhe Scavenger receptor class B, type I (SR-BI), is a high-density lipoprotein (HDL) receptor, which also binds low-density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a coreceptor for hepatitis C virus and a signaling receptor that regulates cell metabolism. Many investigators have reported that lipoproteins bind to SR-BI via a single class of independent (not interacting), high-affinity binding sites (one site model). We have reinvestigated the ligand concentration dependence of [superscript 125]I-HDL binding to SR-BI and SR-BI-mediated specific uptake of [[superscript 3]H]CE from [[superscript 3]H]CE-HDL using an expanded range of ligand concentrations (<1 μg of protein/mL, lower than previously reported). Scatchard and nonlinear least-squares model fitting analyses of the binding and uptake data were both inconsistent with a single class of independent binding sites binding univalent lipoprotein ligands. The data are best fit by models in which SR-BI has either two independent classes of binding sites or one class of sites exhibiting negative cooperativity due to either classic allostery or ensemble effects (“lattice model”). Similar results were observed for LDL. Application of the “infinite dilution” dissociation rate method established that the binding of [superscript 125]I-HDL to SR-BI at 4 °C exhibits negative cooperativity. The unexpected complexity of the interactions of lipoproteins with SR-BI should be taken into account when interpreting the results of experiments that explore the mechanism(s) by which SR-BI mediates ligand binding, lipid transport, and cell signaling. National Institutes of Health (U.S.) 2014-04-07T17:02:39Z 2014-04-07T17:02:39Z 2011-01 2011-01 Article http://purl.org/eprint/type/JournalArticle 0006-2960 1520-4995 http://hdl.handle.net/1721.1/86058 Nieland, Thomas J. F., Shangzhe Xu, Marsha Penman, and Monty Krieger. “Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI.” Biochemistry 50, no. 11 (March 22, 2011): 1818–1830. https://orcid.org/0000-0003-4541-5181 https://orcid.org/0000-0003-2673-1672 en_US http://dx.doi.org/10.1021/bi101657j Biochemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Xu, Shangzhe Krieger, Monty Nieland, Thomas J. Penman, Marsha L. Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI |
| title | Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI |
| title_full | Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI |
| title_fullStr | Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI |
| title_full_unstemmed | Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI |
| title_short | Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI |
| title_sort | negatively cooperative binding of high density lipoprotein to the hdl receptor sr bi |
| url | http://hdl.handle.net/1721.1/86058 https://orcid.org/0000-0003-4541-5181 https://orcid.org/0000-0003-2673-1672 |
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