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Functional duplication of ligand-binding domains within low-density lipoprotein receptor-related protein for interaction with receptor associated protein, α2-macroglobulin, factor IXa and factor VIII

Meijer, Alexander B., Rohlena, Jakub, van der Zwaan, Carmen, van Zonneveld, Anton-Jan, Boertjes, Ria C., Lenting, Peter J., Mertens, Koen·2007·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
DOI 10.1016/j.bbapap.2007.04.003
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Abstract

The low-density lipoprotein receptor-related protein (LRP) binds a range of proteins including receptor associated protein (RAP), activated alpha2-macroglobulin (alpha2M*), factor IXa (FIXa), and factor VIII (FVIII) light chain. The binding is mediated by the complement-type repeats, which are clustered in four distinct regions within LRP. Cluster II of 8 repeats (CR3-10) and cluster IV of 11 repeats (CR21-31) have been implicated in ligand-binding. Previous studies have aimed to identify the cluster II repeats involved in binding alpha2M* and RAP. We now evaluated the binding to RAP, alpha2M*, FIXa and FVIII light chain of triplicate repeat-fragments of not only clusters II but also of cluster IV. Employing surface plasmon resonance analysis, we found that most efficient ligand-binding was displayed by the repeats within region CR4-8 of cluster II and within region CR24-28 of cluster IV. Whereas the binding to RAP could be attributed to two consecutive repeats (CR5-6, CR26-27), combinations of three repeats showed most efficient binding to FIXa (CR6-8, CR26-28), FVIII light chain (CR5-7, CR6-8, CR24-26), and alpha2M* (CR4-6, CR24-26). The results imply that there is an internal functional duplication of complement-type repeats within LRP resulting in two clusters that bind the same ligands.

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Metadata

Authors
Meijer, A. B., Rohlena, J., van der Zwaan, C., van Zonneveld, A.-J., Boertjes, R. C., Lenting, P. J., & Mertens, K.
Venue
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Publisher
Elsevier BV
Published
2007-06
Volume
1774
Issue
6
Pages
714-722
ISSN
1570-9639
DOI
10.1016/j.bbapap.2007.04.003
Cited by
33
References
1
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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