3EDU

Crystal structure of the ankyrin-binding domain of human erythroid spectrin

Summary for 3EDU

• Entry DOI: 10.2210/pdb3edu/pdb
• Descriptor: Spectrin beta chain, erythrocyte (2 entities in total)
• Functional Keywords: spectrin, ankyrin, ankyrin-binding domain, actin capping, actin-binding, cytoskeleton, disease mutation, elliptocytosis, hereditary hemolytic anemia, phosphoprotein, structural protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytoskeleton: P11277
• Total number of polymer chains: 1
• Total formula weight: 24810.54

Authors

Simonovic, M.,Stabach, P.,Simonovic, I.,Steitz, T.A.,Morrow, J.S. (deposition date: 2008-09-03, release date: 2009-02-10, Last modification date: 2024-02-21)

Primary citation

Stabach, P.R.,Simonovic, I.,Ranieri, M.A.,Aboodi, M.S.,Steitz, T.A.,Simonovic, M.,Morrow, J.S.
The structure of the ankyrin-binding site of {beta}-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties
Blood, 113:5377-5384, 2009

PubMed Abstract: Spectrin and ankyrin participate in membrane organization, stability, signal transduction, and protein targeting; their interaction is critical for erythrocyte stability. Repeats 14 and 15 of betaI-spectrin are crucial for ankyrin recognition, yet the way spectrin binds ankyrin while preserving its repeat structure is unknown. We have solved the crystal structure of the betaI-spectrin 14,15 di-repeat unit to 2.1 A resolution and found 14 residues critical for ankyrin binding that map to the end of the helix C of repeat 14, the linker region, and the B-C loop of repeat 15. The tilt (64 degrees) across the 14,15 linker is greater than in any published di-repeat structure, suggesting that the relative positioning of the two repeats is important for ankyrin binding. We propose that a lack of structural constraints on linker and inter-helix loops allows proteins containing spectrin-like di-repeats to evolve diverse but specific ligand-recognition sites without compromising the structure of the repeat unit. The linker regions between repeats are thus critical determinants of both spectrin's flexibility and polyfunctionality. The putative coupling of flexibility and ligand binding suggests a mechanism by which spectrin might participate in mechanosensory regulation.

PubMed: 19168783
DOI: 10.1182/blood-2008-10-184291

Experimental method

X-RAY DIFFRACTION (2.1 Å)