The structure of the ankyrin-binding site of [beta]-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties

Journal Article · Wed Sep 02 04:00:00 EDT 2009 · Blood

DOI:https://doi.org/10.1182/blood-2008-10-184291· OSTI ID:1005784

Stabach, Paul R; Simonovic, Ivana; Ranieri, Miranda A; Aboodi, Michael S; Steitz, Thomas A; Simonovic, Miljan; Morrow, Jon S

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 {beta}I-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 {beta}I-spectrin 14,15 di-repeat unit to 2.1 {angstrom} 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{sup o}) 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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005784
• Journal Information: Blood, Journal Name: Blood Journal Issue: (22) ; 05, 2009 Vol. 113; ISSN BLOOAW; ISSN 0006-4971
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
ERYTHROCYTES
FLEXIBILITY
MEMBRANES
POSITIONING
PROTEINS
RESIDUES
RESOLUTION
STABILITY