Structure-Function Correlations of Calcium Binding and Calcium Channel Activities Based on 3-Dimensional Models of Human Annexins I, II, III, V and VII
| Autor: | Matthew R. Pincus, James M. Chen, Adrian Sheldon |
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| Rok vydání: | 1993 |
| Předmět: |
Models
Molecular Annexins Protein Conformation Molecular Sequence Data chemistry.chemical_element Calcium Protein Structure Secondary Structure-Activity Relationship Structural Biology Annexin Mole Humans Annexin A7 Amino Acid Sequence Calcium ion binding Homology modeling Annexin A5 Annexin A3 Molecular Biology Annexin A2 Annexin A1 chemistry.chemical_classification Binding Sites Chemistry Calcium channel Structure function General Medicine Amino acid Biochemistry Calcium Channels |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 10:1067-1089 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | The annexins are a family of calcium-dependent phospholipid-binding proteins which share a high degree of primary sequence similarity. Using a model of the crystal structure of annexin V as a template, 3-dimensional models of human annexins I, II, III and VII were constructed by homology modeling (J. Greer, J. Mol. Biol. 153, 1027-1042, 1981; J.M. Chen, G. Lee, R.B. Murphy, R.P. Carty, P.W. Brant-Rauf, E. Friedman and M.R. Pincus, J. Biomolec. Str. Dyn. 6, 859-87, 1989) for the 316 amino acid portions corresponding to the annexin V structure published by Huber et al. (J. Mol. Biol. 223, 683-704, 1992). These methods were used to study structure-function correlations for calcium ion binding and calcium channel activity. Published experimental data are specifically shown to be consistent with the annexin models. Possible intramolecular disulfide bridges were identified in annexin I (between Cys297 and Cys316) and in annexins II and VII (between Cys115 and Cys243). Each of the annexin models have 3 postulated calcium binding sites, usually via a Gly-Xxx-Gly-Thr loop with an acidic Glu or Asp residue 42 positions C-terminal to the first Gly. Despite a nonconserved binding site sequence, annexins I and II are able to coordinate calcium in domain 3 since the residue in the second loop position is directed toward the solvent away from the binding pocket. This finding also suggests a mechanism for a conformational change upon binding calcium. Highly conserved Arg and acidic sidechains stabilize the channel pore structure; annexin channels probably exist in a closed state normally. Arg271 may be involved in channel opening upon activation: basic residue 254 can stabilize Glu112, which allows Arg271 to interact with residue 95 instead of Glu112. Residue 267, found on the convex surface at the pore opening, may also be important in modifying channel activity. |
| Databáze: | OpenAIRE |
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