Journal article
The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3
Blood, Vol.110(9), pp.3398-3406
2007
Abstract
The Lutheran blood group glycoprotein, first discovered on erythrocytes, is widely expressed in human tissues. It is a ligand for the α5 subunit of Laminin 511/521, an extracellular matrix protein. This interaction may contribute to vaso-occlusive events that are an important cause of morbidity in sickle cell disease. Using x-ray crystallography, small-angle x-ray scattering, and site-directed mutagenesis, we show that the extracellular region of Lutheran forms an extended structure with a distinctive bend between the second and third immunoglobulin-like domains. The linker between domains 2 and 3 appears to be flexible and is a critical determinant in maintaining an overall conformation for Lutheran that is capable of binding to Laminin. Mutagenesis studies indicate that Asp312 of Lutheran and the surrounding cluster of negatively charged residues in this linker region form the Laminin-binding site. Unusually, receptor binding is therefore not a function of the domains expected to be furthermost from the plasma membrane. These studies imply that structural flexibility of Lutheran may be essential for its interaction with Laminin and present a novel opportunity for the development of therapeutics for sickle cell disease. © 2007 by The American Society of Hematology.
Details
- Title
- The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3
- Authors
- Tosti J Mankelow (Author) - Bristol Institute for Transfusion Sciences, United KingdomNicholas Burton (Author) - University of Bristol, United KingdomFanny O Stefansdottir (Author) - University of Aarhus, United KingdomFrances A Spring (Author) - Cardiff University, United KingdomStephen F Parsons (Author) - Cardiff University, United KingdomJan S Pedersen (Author) - University of Aarhus, United KingdomCristiano L P Oliveira (Author) - University of Aarhus, United KingdomDonna Lammie (Author) - New York Blood Center, United StatesTim J Wess (Author) - Cardiff University, United KingdomNarla Mohandas (Author) - New York Blood Center, United StatesJoel A Chasis (Author) - University of California, United StatesR Leo Brady (Author) - University of Bristol, United KingdomDavid J Anstee (Author) - Bristol Institute for Transfusion Sciences, United Kingdom
- Publication details
- Blood, Vol.110(9), pp.3398-3406
- Publisher
- American Society of Hematology
- Date published
- 2007
- DOI
- 10.1182/blood-2007-06-094748
- ISSN
- 0006-4971
- Organisation Unit
- Office of the Deputy Vice-Chancellor (Academic); University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99451214502621
- Output Type
- Journal article
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- Hematology
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