2pet: Difference between revisions
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
caption="2pet, resolution 1.700Å" /> | caption="2pet, resolution 1.700Å" /> | ||
'''Lutheran glycoprotein, N-terminal domains 1 and 2.'''<br /> | '''Lutheran glycoprotein, N-terminal domains 1 and 2.'''<br /> | ||
==Overview== | |||
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. | |||
==About this Structure== | ==About this Structure== | ||
2PET is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PET OCA]. | 2PET is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PET 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17638854 17638854] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 12: | Line 18: | ||
[[Category: immunoglobulin superfamily.]] | [[Category: immunoglobulin superfamily.]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:43:03 2008'' | ||
Revision as of 10:43, 14 March 2008
|
Lutheran glycoprotein, N-terminal domains 1 and 2.
OverviewOverview
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.
About this StructureAbout this Structure
2PET is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Fri Mar 14 09:43:03 2008