3LBX

Crystal Structure of the Erythrocyte Spectrin Tetramerization Domain Complex

3LBX の概要

• エントリーDOI: 10.2210/pdb3lbx/pdb
• 関連するPDBエントリー: 1AJ3 1OWA 2SPC 3EDV 3F31 3KBT
• 分子名称: Spectrin alpha chain, erythrocyte, Spectrin beta chain, erythrocyte (2 entities in total)
• 機能のキーワード: spectrin, tetramer, complex, three-helix bundle, alpha helix, partial repeat, helical linker, actin capping, actin-binding, cell shape, cytoskeleton, disease mutation, elliptocytosis, hereditary hemolytic anemia, pyropoikilocytosis, sh3 domain, phosphoprotein, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P02549 P11277
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40715.97

構造登録者

Ipsaro, J.J.,Harper, S.L.,Messick, T.E.,Marmorstein, R.,Mondragon, A.,Speicher, D.W. (登録日: 2010-01-08, 公開日: 2010-03-09, 最終更新日: 2024-02-21)

主引用文献

Ipsaro, J.J.,Harper, S.L.,Messick, T.E.,Marmorstein, R.,Mondragon, A.,Speicher, D.W.
Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex.
Blood, 115:4843-4852, 2010

PubMed Abstract: As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrin fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in alpha-spectrin that occur upon binding to beta-spectrin, and it reports the first structure of the beta-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.

PubMed: 20197550
DOI: 10.1182/blood-2010-01-261396

実験手法

X-RAY DIFFRACTION (2.8 Å)