Interconversion between two unrelated protein folds in the lymphotactin native state
| Autor: | Snjezana Kutlesa, Robbyn L. Tuinstra, Michael A. Kron, Brian F. Volkman, E. Sonay Elgin, Francis C. Peterson |
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| Přispěvatelé: | MÜ, Fen Fakültesi, Kimya Bölümü, Sonay Elgin, Emine |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Conformational change XCR1 Lymphokines Protein Denaturation Protein Folding Multidisciplinary Stereochemistry Chemistry Sialoglycoproteins chemokine Nuclear magnetic resonance spectroscopy Biological Sciences Protein Structure Tertiary Protein structure conformational change NMR spectroscopy Native state Humans Protein folding Protein Structure Quaternary Peptide sequence Dimerization Nuclear Magnetic Resonance Biomolecular XCL1 |
| Popis: | WOS: 000254723700020 PubMed ID: 18364395 Proteins often have multiple functional states, which might not always be accommodated by a single fold. Lymphotactin (Ltn) adopts two distinct structures in equilibrium, one corresponding to the canonical chemokine fold consisting of a monomeric three-stranded P-sheet and carboxyl-terminal helix. The second Ltn structure solved by NMR reveals a dimeric all-beta-sheet arrangement with no similarity to other known proteins. In physiological solution conditions, both structures are significantly populated and interconvert rapidly. Interconversion replaces long-range interactions that stabilize the chemokine fold with an entirely new set of tertiary and quaternary contacts. The chemokine-like Ltn conformation is a functional XCR1 agonist, but fails to bind heparin. In contrast, the alternative structure binds glycosaminoglycans with high affinity but fails to activate XCR1. Because each structural species displays only one of the two functional properties essential for activity in vivo, the conformational equilibrium is likely to be essential for the biological activity of lymphotactin. These results demonstrate that the functional repertoire and regulation of a single naturally occurring amino acid sequence can be expanded by access to a set of highly dissimilar native-state structures. NIAID NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01 AI045843, R01 AI063325-01, R01 AI45843, R01 AI063325, UO1 AI053877, R01 AI063325-02, U01 AI053877, R01 AI063325-03, R01 AI063325-04] Funding Source: Medline; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI063325, U01AI053877, R01AI045843, U01AI053877, R01AI063325, R01AI063325, U01AI053877, R01AI045843, R01AI045843, U01AI053877, R01AI063325, R01AI045843, R01AI063325, U01AI053877, R01AI063325, U01AI053877] Funding Source: NIH RePORTER |
| Databáze: | OpenAIRE |
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