Structural basis for spectrin recognition by ankyrin

Journal Article · Tue Oct 19 04:00:00 EDT 2010 · Blood

DOI:https://doi.org/10.1182/blood-2009-11-255604· OSTI ID:1002752

Ipsaro, Jonathan J; Mondragón, Alfonso ^[1]

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1. NWU

Maintenance of membrane integrity and organization in the metazoan cell is accomplished through intracellular tethering of membrane proteins to an extensive, flexible protein network. Spectrin, the principal component of this network, is anchored to membrane proteins through the adaptor protein ankyrin. To elucidate the atomic basis for this interaction, we determined a crystal structure of human {beta}I-spectrin repeats 13 to 15 in complex with the ZU5-ANK domain of human ankyrin R. The structure reveals the role of repeats 14 to 15 in binding, the electrostatic and hydrophobic contributions along the interface, and the necessity for a particular orientation of the spectrin repeats. Using structural and biochemical data as a guide, we characterized the individual proteins and their interactions by binding and thermal stability analyses. In addition to validating the structural model, these data provide insight into the nature of some mutations associated with cell morphology defects, including those found in human diseases such as hereditary spherocytosis and elliptocytosis. Finally, analysis of the ZU5 domain suggests it is a versatile protein-protein interaction module with distinct interaction surfaces. The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002752
• Journal Information: Blood, Journal Name: Blood Journal Issue: (20) ; 05, 2010 Vol. 115; ISSN BLOOAW; ISSN 0006-4971
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DEFECTS
DISEASES
ELECTROSTATICS
MAINTENANCE
MEMBRANE PROTEINS
MEMBRANES
MORPHOLOGY
MUTATIONS
ORIENTATION
PROTEINS
STABILITY
STRUCTURAL MODELS