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; Zwaan, Carmen van der; Zonneveld, Anton Jan van; Boertjes, Ria; Lenting, Peter J.; Mertens, Koen

doi:10.1016/j.bbapap.2007.04.003

Cited by 38 publications

(67 citation statements)

References 45 publications

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“…The LDLR fragments obtained were essentially pure (Fig. 1); the observed double banding for some of the CR doublets was attributed to a possible difference in glycosylation, similar to that found previously for expressed fragments of LRP (31).…”

Section: Expression Of Ldlr Fragments-supporting

confidence: 83%

“…Although fitting of the signals was not optimal, similar to that found for FVIII and LRP (41), the respective kinetic constants including K D values (30 -60 nM) were assessed as similar (supplemental Table S2). These data indicated that the LDLR cluster contains all required elements to bind FVIII, similar to that found for LRP clusters (31). Among the CR doublets, CR.2-3, CR.3-4, and CR.4-5 were found active for FVIII (Fig.…”

Section: Expression Of Ldlr Fragments-supporting

confidence: 76%

“…As RAP is a common ligand of the LDLR family, it is worthwhile to compare its binding sites between the receptors. In LRP cluster II, the RAP-binding region is presented by seven adjacent CRs and comprises the sites for other ligands (30,31,37,61). In LDLR, the RAP-binding region comprises the sites for FVIII (present study) and apoE (CR.4-5) (27), whereas a longer region involving CR.3-7 and an EGF-like repeat is required for apoB-100 (28,62).…”

Section: Discussionmentioning

confidence: 88%

“…In a series of studies by Mertens and co-workers (2,64,65), it was shown that the CR clusters of LDLR and LRP compete for binding to FVIII. Within each of the LRP clusters II and IV, approximately four adjacent CRs form a binding site for FVIII (31,33), whereas the matching epitope of FVIII involves multiple lysines on all three domains of its light chain (65)(66)(67)(68). Consistent with this, the anti-FVIII ScFv KM33, which recognizes the C1-domain of the light chain, interferes with FVIII binding to both LDLR and LRP (46,48,69).…”

Section: Discussionmentioning

confidence: 99%

“…For FVIII, LRP has two binding sites; each site is formed by 3-4 adjacent CRs and located in a separate CR cluster of the receptor (31,32). At the same time, the FVIII-binding site in LDLR is unknown.…”

Section: Factor VIII (Fviii)mentioning

confidence: 99%

See 4 more Smart Citations

Mapping the Binding Region on the Low Density Lipoprotein Receptor for Blood Coagulation Factor VIII

Kurasawa

Shestopal

Karnaukhova

et al. 2013

Journal of Biological Chemistry

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Background: Low density lipoprotein receptor (LDLR) mediates clearance of blood coagulation factor VIII (FVIII). Results:The region of complement-type repeats 2-5 in LDLR was identified as the binding site for FVIII and for ␣-2-macroglobulin receptor-associated protein (RAP). Conclusion: Binding sites of LDLR for FVIII, and also for RAP, were characterized. Significance: This provides new data on LDLR structure and function and on FVIII catabolism.

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Section: Expression Of Ldlr Fragments-supporting

confidence: 83%

Section: Expression Of Ldlr Fragments-supporting

confidence: 76%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Factor VIII (Fviii)mentioning

confidence: 99%

See 3 more Smart Citations

Mapping the Binding Region on the Low Density Lipoprotein Receptor for Blood Coagulation Factor VIII

Kurasawa

Shestopal

Karnaukhova

et al. 2013

Journal of Biological Chemistry

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Diversification and coevolution of the ghrelin/growth hormone secretagogue receptor system in vertebrates

Tine

Kuhl

Teske

et al. 2016

Ecology and Evolution

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The gut hormone ghrelin is involved in numerous metabolic functions, such as the stimulation of growth hormone secretion, gastric motility, and food intake. Ghrelin is modified by ghrelin O‐acyltransferase (GOAT) or membrane‐bound O‐acyltransferase domain‐containing 4 (MBOAT4) enabling action through the growth hormone secretagogue receptors (GHS‐R). During the course of evolution, initially strong ligand/receptor specificities can be disrupted by genomic changes, potentially modifying physiological roles of the ligand/receptor system. Here, we investigated the coevolution of ghrelin, GOAT, and GHS‐R in vertebrates. We combined similarity search, conserved synteny analyses, phylogenetic reconstructions, and protein structure comparisons to reconstruct the evolutionary history of the ghrelin system. Ghrelin remained a single‐gene locus in all vertebrate species, and accordingly, a single GHS‐R isoform was identified in all tetrapods. Similar patterns of the nonsynonymous (dN) and synonymous (dS) ratio (dN/dS) in the vertebrate lineage strongly suggest coevolution of the ghrelin and GHS‐R genes, supporting specific functional interactions and common physiological pathways. The selection profiles do not allow confirmation as to whether ghrelin binds specifically to GOAT, but the ghrelin dN/dS patterns are more similar to those of GOAT compared to MBOAT1 and MBOAT2 isoforms. Four GHS‐R isoforms were identified in teleost genomes. This diversification of GHS‐R resulted from successive rounds of duplications, some of which remained specific to the teleost lineage. Coevolution signals are lost in teleosts, presumably due to the diversification of GHS‐R but not the ghrelin gene. The identification of the GHS‐R diversity in teleosts provides a molecular basis for comparative studies on ghrelin's physiological roles and regulation, while the comparative sequence and structure analyses will assist translational medicine to determine structure–function relationships of the ghrelin/GHS‐R system.

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Survey of the year 2007 commercial optical biosensor literature

Rich

Myszka

2008

J of Molecular Recognition

163

121

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In 2007, 1179 papers were published that involved the application of optical biosensors. Reported developments in instrument hardware, assay design, and immobilization chemistry continue to improve the technology's throughput, sensitivity, and utility. Compared to recent years, the widest range of platforms, both traditional format and array-based, were used. However, as in the past, we found a disappointingly low percentage of well-executed experiments and thoughtful data interpretation. We are alarmed by the high frequency of suboptimal data and over-interpreted results in the literature. Fortunately, learning to visually recognize good--and more importantly, bad--data is easy. Using examples from the literature, we outline several features of biosensor responses that indicate experimental artifacts versus actual binding events. Our goal is to have everyone, from benchtop scientists to project managers and manuscript reviewers, become astute judges of biosensor results using nothing more than their eyes.

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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

Cited by 38 publications

References 45 publications

Mapping the Binding Region on the Low Density Lipoprotein Receptor for Blood Coagulation Factor VIII

Mapping the Binding Region on the Low Density Lipoprotein Receptor for Blood Coagulation Factor VIII

Diversification and coevolution of the ghrelin/growth hormone secretagogue receptor system in vertebrates

Survey of the year 2007 commercial optical biosensor literature

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