| Probing the caveolin-1 P132L mutant: critical insights into its oligomeric behavior and structure. | |
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MedLine Citation:
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PMID: 22506673 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Caveolin-1 is the most important protein found in caveolae, which are cell surface invaginations of the plasma membrane that act as signaling platforms. A single point mutation in the transmembrane domain of caveolin-1 (proline 132 to leucine) has deleterious effects on caveolae formation in vivo and has been implicated in various disease states, particularly aggressive breast cancers. Using a combination of gel filtration chromatography and analytical ultracentrifugation, we found that a fully functional construct of caveolin-1 (Cav1(62-178)) was a monomer in dodecylphosphocholine micelles. In contrast, the P132L mutant of Cav1(62-178) was dimeric. To explore the dimerization of the P132L mutant further, various truncated constructs (Cav1(82-178), Cav1(96-178), Cav1(62-136), Cav1(82-136), Cav1(96-136)) were prepared which revealed that oligomerization occurs in the transmembrane domain (residues 96-136) of caveolin-1. To characterize the mutant structurally, solution-state NMR experiments in lyso-myristoylphosphatidylglycerol were undertaken of the Cav1(96-136) P132L mutant. Chemical shift analysis revealed that, compared to the wild-type, helix 2 in the transmembrane domain was lengthened by four residues (wild-type, residues 111-129; mutant, residues 111-133), which corresponds to an extra turn in helix 2 of the mutant. Lastly, point mutations at position 132 of Cav1(62-178) (P132A, P132I, P132V, P132G, P132W, P132F) revealed that no other hydrophobic amino acid can preserve the monomeric state of Cav1(62-178), which indicates that proline 132 is critical in supporting proper caveolin-1 behavior. |
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Authors:
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Monica D Rieth; Jinwoo Lee; Kerney Jebrell Glover |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-04-25 |
Journal Detail:
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Title: Biochemistry Volume: 51 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-08 Completed Date: 2012-07-09 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
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Languages: eng Pagination: 3911-8 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Lehigh University, 6 E. Packer Ave, Bethlehem, Pennsylvania 18015, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Caveolin 1
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chemistry,
genetics*,
metabolism Cell Membrane / metabolism Humans Nuclear Magnetic Resonance, Biomolecular Point Mutation Proline / chemistry, genetics Protein Multimerization Protein Structure, Tertiary Ultracentrifugation |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM093258/GM/NIGMS NIH HHS; R01 GM093258-01A1/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Caveolin 1; 147-85-3/Proline |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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