Recognition of <i>Dictyostelium discoideum</i> Lysosomal Enzymes Is Conferred by the Amino-Terminal Carbohydrate Binding Site of the Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor

Marron-Terada, Patricia G.; Hancock, Michael K.; Haskins, Darin J.; Dahms, Nancy M.

doi:10.1021/bi992226o

Cited by 40 publications

(55 citation statements)

References 50 publications

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“…contain M6P, as a component of the cell wall, teichoic acids, lipoteichoic acids, or other virulence factors, that is available to interact with IGFIIR during pathogenesis. The carbohydrate binding site of the IGFIIR in domain 3 has been shown to recognize related structures such as phosphodiesters or mannose 6-sulfate (54,55,81), and the interaction of Listeria spp. with the IGFIIR may be based on such a related structure that is present on the cell surface of Listeria bacteria.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

et al. 2006

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The gram-positive bacterium Listeria monocytogenes causes a life-threatening disease known as listeriosis. The mechanism by which L. monocytogenes invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor CI M6PR or CD222) as a novel receptor for binding and invasion of Listeria species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized L. monocytogenes cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All Listeria spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by L. monocytogenes and L. innocua was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of Listeria spp. as affinity matrices. Adherence to and invasion of mammalian cells by L. monocytogenes was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of L. monocytogenes of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by L. monocytogenes may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.The gram-positive bacterium Listeria monocytogenes is a human pathogen that causes listeriosis primarily in immunosuppressed individuals. Symptoms are flu-like, and yet disease may progress to severe complications such as meningitis, septicemia, spontaneous abortion, or listeriosis of the newborn (28,39,83). The number of cases of listeriosis range from 40 to 44 per year in Australia (3, 79) and average 100 per year in the United States (13). Although the incidence of listeriosis is low compared to that of other foodborne diseases, the associated mortality rate is high (approximately 30%) (39, 74, 83). Knowledge of the molecular mechanisms underlying the binding and internalization of Listeria spp. to host cells is limited. New antibiotic, vaccine, and diagnostic targets are needed to prevent and treat infection by Listeria spp., and understanding the processes of adherence and entry into cells is fundamental to defining appropriate preventative and therapeutic strategies.Random peptide phage display has been successfully employed to identify new receptors and receptor ligands (44,52,53,82) and in epitope mapping and mimicking of protein antigens and antibodies (16,42,61) and drug discovery (40,52,78). In this study we employed random peptide phage display in an attempt to identify novel surface antigens that may be used as therapeutic targets ...

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Section: Discussionmentioning

confidence: 99%

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

et al. 2006

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“…IGF-IIR is exposed to a range of pH environments in vivo, since it is involved in ligand internalization at the cell surface, protein sorting within the trans-Golgi network and transport to the endosomes (53). The membrane-bound receptor binds mannosylated proteins with maximal binding within a pH range of 6.5-7.5, and optimum binding of ␤-glucuronidase to domains 1-3 and 7-9 occurs at pH 6.9 and 6.4 -6.5, respectively (50,51). In addition, the 46-kDa cation-dependent mannose 6-phosphate receptor, which displays sequence similarity to each extracytoplasmic domain of IGF-IIR, displays weak binding at neutral pH and has a pH optimum at 6.0 -6.3 (54).…”

Section: Discussionmentioning

confidence: 99%

Real Time Kinetics of Insulin-like Growth Factor II (IGF-II) Interaction with the IGF-II/Mannose 6-Phosphate Receptor

Linnell¹,

Groeger

Hassan³

2001

Journal of Biological Chemistry

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The interaction of soluble forms of the human cationindependent insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-IIR) with IGFs and mannosylated ligands was analyzed in real time. IGF-IIR proteins containing domains 1-15, 10 -13, 11-13, or 11-12 were combined with rat CD4 domains 3 and 4. Following transient expression in 293T cells, secreted protein was immobilized onto biosensor chips. ␤-Glucuronidase and latent transforming growth factor-␤1 bound only to domains 1-15. IGF-II bound to all constructs except a control, which contained a point mutation in domain 11. The affinity of domains 1-15, 10 -13, 11-13, and 11-12 to IGF-II were 14, 120, 100, and 450 nM, respectively. Our data suggest that domain 13 acts as an enhancer of IGF-II affinity by slowing the rate of dissociation, but additional enhancement by domains other than 10 -13 also occurs. As the receptor functions to transport ligands from either the trans-Golgi network or extracellular space to the endosomes, the interaction of IGF-IIR extracellular domains with IGF-II was analyzed over a pH range of 5.0 -7.4. The constructs behaved differently in response to pH and in recovery after low pH exposure, suggesting that pH stability of the extracellular domains depends on domains other than 10 -13.

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“…This receptor contains three Man-6-P-binding sites (in domains 1-3, 5, and 9) that differ in their affinities for Man-6-P and in their specificity, with domain 9 exhibiting high specificity for phosphomonoesters and domains 1-3 capable of efficiently binding phosphodiesters as well as phosphomonoesters (Fig. 9B) (35). Evidence from several laboratories indicates that the CI-MPR exists as an oligomer, most likely as a dimer (14,41,42).…”

Section: Discussionmentioning

confidence: 99%

“…The reaction was quenched by the addition of glycine to 100 mM. The samples were resolved by SDS-PAGE followed by Western blotting as described previously (35), except that the proteins were detected using an anti-tetrahistidine monoclonal antibody (QIAGEN Inc.) followed by horseradish peroxidase-linked goat anti-mouse antibody (Amersham Biosciences).…”

Section: Matrix-assisted Laser Desorption Ionization Time-of-flight Mmentioning

confidence: 99%

Identification of a Low Affinity Mannose 6-Phosphate-binding Site in Domain 5 of the Cation-independent Mannose 6-Phosphate Receptor

Reddy

Chai

Childs

et al. 2004

Journal of Biological Chemistry

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The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) and the 46-kDa cation-dependent MPR (CD-MPR) are type I integral membrane glycoproteins that play a critical role in the intracellular delivery of newly synthesized mannose 6-phosphate (Man-6-P)-containing acid hydrolases to the lysosome. The extracytoplasmic region of the CI-MPR contains 15 contiguous domains, and the two high affinity (ϳ1 nM) Man-6-P-binding sites have been mapped to domains 1-3 and 9, with essential residues localized to domains 3 and 9. Domain 5 of the CI-MPR exhibits significant sequence homology to domains 3 and 9 as well as to the CD-MPR. A structure-based sequence alignment was performed that predicts that domain 5 contains the four conserved key residues (Gln, Arg, Glu, and Tyr) identified as essential for carbohydrate recognition by the CD-MPR and domains 3 and 9 of the CI-MPR, but lacks two cysteine residues predicted to form a disulfide bond within the binding pocket. To determine whether domain 5 harbors a carbohydrate-binding site, a construct that encodes domain 5 alone (Dom5His) was expressed in Pichia pastoris. Microarray analysis using 30 different oligosaccharides demonstrated that Dom5His bound specifically to a Man-6-P-containing oligosaccharide (pentamannosyl 6-phosphate). Frontal affinity chromatography showed that the affinity of Dom5His for Man-6-P was ϳ300-fold lower (K i ‫؍‬ 5.3 mM) than that observed for domains 1-3 and 9. The interaction affinity for the lysosomal enzyme ␤-glucuronidase was also much lower (K d ‫؍‬ 54 M) as determined by surface plasmon resonance analysis. Taken together, these results demonstrate that the CI-MPR contains a third Man-6-P recognition site that is located in domain 5 and that exhibits lower affinity than the carbohydrate-binding sites present in domains 1-3 and 9.

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Recognition of Dictyostelium discoideum Lysosomal Enzymes Is Conferred by the Amino-Terminal Carbohydrate Binding Site of the Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor

Cited by 40 publications

References 50 publications

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

Real Time Kinetics of Insulin-like Growth Factor II (IGF-II) Interaction with the IGF-II/Mannose 6-Phosphate Receptor

Identification of a Low Affinity Mannose 6-Phosphate-binding Site in Domain 5 of the Cation-independent Mannose 6-Phosphate Receptor

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