2pet

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{{STRUCTURE_2pet| PDB=2pet | SCENE= }}
{{STRUCTURE_2pet| PDB=2pet | SCENE= }}
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'''Lutheran glycoprotein, N-terminal domains 1 and 2.'''
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===Lutheran glycoprotein, N-terminal domains 1 and 2.===
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==Overview==
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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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{{ABSTRACT_PUBMED_17638854}}
==About this Structure==
==About this Structure==
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[[Category: Cell adhesion]]
[[Category: Cell adhesion]]
[[Category: Immunoglobulin superfamily.]]
[[Category: Immunoglobulin superfamily.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:58:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:09:23 2008''

Revision as of 12:09, 28 July 2008

Image:2pet.png

Template:STRUCTURE 2pet

Lutheran glycoprotein, N-terminal domains 1 and 2.

Template:ABSTRACT PUBMED 17638854

About this Structure

2PET is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3., Mankelow TJ, Burton N, Stefansdottir FO, Spring FA, Parsons SF, Pedersen JS, Oliveira CL, Lammie D, Wess T, Mohandas N, Chasis JA, Brady RL, Anstee DJ, Blood. 2007 Nov 1;110(9):3398-406. Epub 2007 Jul 17. PMID:17638854

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