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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Park, S. Articles by Fung, L. W.-M. Search for Related Content PubMed PubMed Citation Articles by Park, S. Articles by Fung, L. W.-M. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2002, Vol. 100, No. 1, pp. 283-288 RED CELLS Nuclear magnetic resonance studies of mutations at the tetramerization region of human alpha spectrin Sunghyouk Park, Michael E. Johnson, and Leslie W.-M. Fung From the Center for Pharmaceutical Biotechnology, University of Illinois at Chicago; and the Department of Chemistry, Loyola University of Chicago, IL. Many spectrin mutations that destabilize tetramer formation and lead to hereditary hemolytic anemias are located at the N-terminal region of -spectrin, with the Arg28 position considered to be a mutation hot spot. We have introduced mutations at positions 28 and 45 into a model peptide, Sp1-156, consisting of the first 156 residues in the N-terminal region of -spectrin (N). The association of these -spectrin peptides that have single amino acid replacements with a -spectrin model peptide, consisting of the C-terminal region of -spectrin (C), was determined, and structural changes due to amino acid replacements were monitored by nuclear magnetic resonance (NMR). We found evidence for similar and very localized structural changes in Sp1-156Arg45Thr and Sp1-156Arg45Ser, although these 2 mutant peptides associated with -spectrin peptide with significantly differing affinities. The Sp1-156Arg28Ser peptide showed an affinity for the -spectrin peptide comparable to that of Sp1-156Arg45Ser, but it exhibited substantial and widespread spectral changes. Our results suggest that both Arg45 replacements induce only minor structural perturbations in the first helix of Sp1-156, but the Arg28Ser replacement affects both the first helix and the following structural domain. Our results also indicate that the mechanism for reduced spectrin tetramerization is through mutation-induced changes in molecular recognition at the -tetramerization site, rather than through conformational disruption, as has been suggested in prior literature. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Gaetani, S. Mootien, S. Harper, P. G. Gallagher, and D. W. Speicher Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site Blood, June 15, 2008; 111(12): 5712 - 5720. [Abstract] [Full Text] [PDF] F. Long, D. McElheny, S. Jiang, S. Park, M. S. Caffrey, and L. W.-M. Fung Conformational change of erythroid {alpha}-spectrin at the tetramerization site upon binding beta-spectrin Protein Sci., November 1, 2007; 16(11): 2519 - 2530. [Abstract] [Full Text] [PDF] S. Park, M. S. Caffrey, M. E. Johnson, and L. W.-M. Fung Solution Structural Studies on Human Erythrocyte {alpha}-Spectrin Tetramerization Site J. Biol. Chem., June 6, 2003; 278(24): 21837 - 21844. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020