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PDBsum entry 2pf6
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Cell adhesion
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PDB id
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2pf6
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References listed in PDB file
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Key reference
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Title
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The laminin 511/521-Binding site on the lutheran blood group glycoprotein is located at the flexible junction of ig domains 2 and 3.
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Authors
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T.J.Mankelow,
N.Burton,
F.O.Stefansdottir,
F.A.Spring,
S.F.Parsons,
J.S.Pedersen,
C.L.Oliveira,
D.Lammie,
T.Wess,
N.Mohandas,
J.A.Chasis,
R.L.Brady,
D.J.Anstee.
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Ref.
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Blood, 2007,
110,
3398-3406.
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PubMed id
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Abstract
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The Lutheran blood group glycoprotein, first discovered on erythrocytes, is
widely expressed in human tissues. It is a ligand for the alpha5 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.
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