scholarly journals Multiple interactions between pituitary hormones and the mannose receptor

1999 ◽  
Vol 343 (2) ◽  
pp. 403-411 ◽  
Author(s):  
Daniel Z. SIMPSON ◽  
Paul G. HITCHEN ◽  
Elizabeth L. ELMHIRST ◽  
Maureen E. TAYLOR
Keyword(s):  
Ionic Strength ◽  
Binding Site ◽  
Specific Binding ◽  
Mannose Receptor ◽  
Pituitary Hormones ◽  
Pituitary Hormone ◽  
Truncated Form ◽  
Additional Function ◽  
Rich Domain ◽  
Cysteine Rich Domain

The macrophage mannose receptor, which has a well-documented role in the innate immune system, has an additional function in the clearance of pituitary hormones. Clearance is mediated by the recognition of sulphated terminal N-acetylgalactosamine residues (SO4-4GalNAc) on the hormones. Previous studies with an SO4-4GalNAc-containing neoglycoprotein suggest that the SO4-4GalNAc-binding site is localized to the N-terminal cysteine-rich domain of the receptor, distinct from the mannose/N-acetylglucosamine/fucose-specific C-type carbohydrate-recognition domains (CRDs). The present study characterizes the binding of natural pituitary hormone ligands to a soluble portion of the mannose receptor consisting of the whole extracellular domain and to a truncated form containing the eight CRDs but lacking the N-terminal cysteine-rich domain and the fibronectin type II repeat. Both forms of the receptor show high-affinity saturable binding of lutropin and thyrotropin. Binding to the full-length receptor is dependent on pH and ionic strength and is inhibited effectively by SO4-4GalNAc but only partly by mannose. In contrast, binding to the truncated form of the receptor, which is also dependent on pH and ionic strength, is inhibited by mannose but not by SO4-4GalNAc. The results are consistent with the presence of an SO4-4GalNAc-specific binding site in the cysteine-rich domain of the mannose receptor but indicate that interactions between other sugars on the hormones and the CRDs are also important in hormone binding.

scholarly journals Crystal Structure of the Cysteine-Rich Domain of Mannose Receptor Complexed with a Sulfated Carbohydrate Ligand

2000 ◽  
Vol 191 (7) ◽  
pp. 1105-1116 ◽  
Author(s):  
Yang Liu ◽  
Arthur J. Chirino ◽  
Ziva Misulovin ◽  
Christine Leteux ◽  
Ten Feizi ◽  
...  
Keyword(s):  
Mannose Receptor ◽  
Pituitary Hormones ◽  
Carbohydrate Binding ◽  
Fibroblast Growth ◽  
The Third ◽  
Rich Domain ◽  
Sulfated Carbohydrate ◽  
Carbohydrate Ligand ◽  
Macrophage Uptake ◽  
Cysteine Rich Domain

The macrophage and epithelial cell mannose receptor (MR) binds carbohydrates on foreign and host molecules. Two portions of MR recognize carbohydrates: tandemly arranged C-type lectin domains facilitate carbohydrate-dependent macrophage uptake of infectious organisms, and the NH2-terminal cysteine-rich domain (Cys-MR) binds to sulfated glycoproteins including pituitary hormones. To elucidate the mechanism of sulfated carbohydrate recognition, we determined crystal structures of Cys-MR alone and complexed with 4-sulfated-N-acetylgalactosamine at 1.7 and 2.2 Å resolution, respectively. Cys-MR folds into an approximately three-fold symmetric β-trefoil shape resembling fibroblast growth factor. The sulfate portions of 4-sulfated-N-acetylgalactosamine and an unidentified ligand found in the native crystals bind in a neutral pocket in the third lobe. We use the structures to rationalize the carbohydrate binding specificities of Cys-MR and compare the recognition properties of Cys-MR with other β-trefoil proteins.

scholarly journals The Cysteine-Rich Domain of the Macrophage Mannose Receptor Is a Multispecific Lectin That Recognizes Chondroitin Sulfates a and B and Sulfated Oligosaccharides of Blood Group Lewisa and Lewisx Types in Addition to the Sulfated N-Glycans of Lutropin

2000 ◽  
Vol 191 (7) ◽  
pp. 1117-1126 ◽  
Author(s):  
Christine Leteux ◽  
Wengang Chai ◽  
R. Wendy Loveless ◽  
Chun-Ting Yuen ◽  
Lars Uhlin-Hansen ◽  
...  
Keyword(s):  
Blood Group ◽  
Retinal Pigment ◽  
Mannose Receptor ◽  
Pituitary Hormones ◽  
Germinal Centers ◽  
Retinal Pigment Epithelial Cells ◽  
Microbial Pathogens ◽  
Rich Domain ◽  
Sulfated Carbohydrate ◽  
Cysteine Rich Domain

The mannose receptor (MR) is an endocytic protein on macrophages and dendritic cells, as well as on hepatic endothelial, kidney mesangial, tracheal smooth muscle, and retinal pigment epithelial cells. The extracellular portion contains two types of carbohydrate-recognition domain (CRD): eight membrane-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR). The former bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, and may be important in innate immunity towards microbial pathogens, and in antigen trapping for processing and presentation in adaptive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitary hormones and may have a role in hormonal clearance. A second feature of Cys-MR is binding to macrophages in marginal zones of the spleen, and to B cell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel classes of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of the type found on proteoglycans produced by cells of the immune system, and sulfated blood group chains. We further demonstrate that Cys-MR interacts with cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may variously regulate the trafficking and function of MR-bearing cells.

scholarly journals The Membrane-proximal Scavenger Receptor Cysteine-rich Domain of CD6 Contains the Activated Leukocyte Cell Adhesion Molecule Binding Site

1995 ◽  
Vol 270 (31) ◽  
pp. 18187-18190 ◽  
Author(s):  
Gena S. Whitney ◽  
Gary C. Starling ◽  
Michael A. Bowen ◽  
Brett Modrell ◽  
Anthony W. Siadak ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Binding Site ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Scavenger Receptor ◽  
Rich Domain ◽  
Cysteine Rich Domain

scholarly journals Structural and Functional Characterization of an Anesthetic Binding Site in the Second Cysteine-Rich Domain of Protein Kinase Cδ∗

2012 ◽  
Vol 103 (11) ◽  
pp. 2331-2340 ◽  
Author(s):  
Sivananthaperumal Shanmugasundararaj ◽  
Joydip Das ◽  
Warren S. Sandberg ◽  
Xiaojuan Zhou ◽  
Dan Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Binding Site ◽  
Functional Characterization ◽  
Rich Domain ◽  
Cysteine Rich Domain ◽  
Protein Kinase Cδ

scholarly journals Mannose-Binding Lectin Binds to Amyloid Protein and Modulates Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mykol Larvie ◽  
Timothy Shoup ◽  
Wei-Chuan Chang ◽  
Lorencia Chigweshe ◽  
Kevan Hartshorn ◽  
...  
Keyword(s):  
Mannose Receptor ◽  
Tissue Homeostasis ◽  
Mannose Binding Lectin ◽  
Binding Characteristics ◽  
Calcium Dependent ◽  
Rich Domain ◽  
Mannose Binding ◽  
Carbohydrate Ligands ◽  
Binding Lectin ◽  
Cysteine Rich Domain

Mannose-binding lectin (MBL), a soluble factor of the innate immune system, is a pattern recognition molecule with a number of known ligands, including viruses, bacteria, and molecules from abnormal self tissues. In addition to its role in immunity, MBL also functions in the maintenance of tissue homeostasis. We present evidence here that MBL binds to amyloidβpeptides. MBL binding to other known carbohydrate ligands is calcium-dependent and has been attributed to the carbohydrate-recognition domain, a common feature of other C-type lectins. In contrast, we find that the features of MBL binding to Aβare more similar to the reported binding characteristics of the cysteine-rich domain of the unrelated mannose receptor and therefore may involve the MBL cysteine-rich domain. Differences in MBL ligand binding may contribute to modulation of inflammatory response and may correlate with the function of MBL in processes such as coagulation and tissue homeostasis.

scholarly journals The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.

1996 ◽  
Vol 93 (16) ◽  
pp. 8312-8317 ◽  
Author(s):  
H. R. Mott ◽  
J. W. Carpenter ◽  
S. Zhong ◽  
S. Ghosh ◽  
R. M. Bell ◽  
...  
Keyword(s):  
Binding Site ◽  
Solution Structure ◽  
Phospholipid Binding ◽  
Rich Domain ◽  
Cysteine Rich Domain

scholarly journals Expression of mannose receptor and ligands for its cysteine-rich domain in venous sinuses of human spleen

2005 ◽  
Vol 85 (10) ◽  
pp. 1238-1249 ◽  
Author(s):  
Luisa Martinez-Pomares ◽  
Leif G Hanitsch ◽  
Richard Stillion ◽  
Satish Keshav ◽  
Siamon Gordon
Keyword(s):  
Mannose Receptor ◽  
Human Spleen ◽  
Venous Sinuses ◽  
Rich Domain ◽  
Cysteine Rich Domain

scholarly journals Function of the cysteine-rich domain of the haemorrhagic metalloproteinase atrolysin A: targeting adhesion proteins collagen I and von Willebrand factor

2005 ◽  
Vol 391 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Solange M. T. Serrano ◽  
Li-Guo Jia ◽  
Deyu Wang ◽  
John D. Shannon ◽  
Jay W. Fox
Keyword(s):  
Binding Site ◽  
Von Willebrand Factor ◽  
Solid Phase ◽  
Collagen I ◽  
Cell Surface Receptor ◽  
Receptor Binding Site ◽  
Rich Domain ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Cysteine Rich Domain

The cysteine-rich domain of the haemorrhagic metalloproteinase atrolysin A was shown to inhibit collagen-stimulated platelet aggregation and to interact with MG-63 osteosarcoma cells via integrin α2β1 to inhibit adhesion to collagen I. In addition, we demonstrate by solid-phase binding assays that atrolysin A binds to collagen I and to vWF (von Willebrand factor) via exosites in the cysteine-rich domain. Interestingly, the binding site of the cysteine-rich domain on collagen I is distinct from the cell adhesion site, since the incubation of collagen-I-coated plates with the cysteine-rich domain did not prevent the adhesion of MG-63 cells to collagen. Finally, we show by surface plasmon resonance (BIAcore™) analyses that the cysteine-rich domain can block vWF binding to collagen I as well as the binding of collagen I to vWF. Taken together, these results indicate that this domain may function as a cell-surface-receptor-binding site and/or a substrate recognition exosite and may thus play a role in the pathologies associated with atrolysin A.

scholarly journals The RafC1 Cysteine-Rich Domain Contains Multiple Distinct Regulatory Epitopes Which Control Ras-Dependent Raf Activation

1998 ◽  
Vol 18 (11) ◽  
pp. 6698-6710 ◽  
Author(s):  
Martina Daub ◽  
Johannes Jöckel ◽  
Thomas Quack ◽  
Christoph K. Weber ◽  
Frank Schmitz ◽  
...  
Keyword(s):  
Binding Site ◽  
Positive Function ◽  
Negative Control ◽  
Cofactor Binding ◽  
Activating Mutations ◽  
Rich Domain ◽  
Absolute Requirement ◽  
High Resolution Map ◽  
Cysteine Rich Domain

ABSTRACT Activation of c-Raf-1 (referred to as Raf) by Ras is a pivotal step in mitogenic signaling. Raf activation is initiated by binding of Ras to the regulatory N terminus of Raf. While Ras binding to residues 51 to 131 is well understood, the role of the RafC1 cysteine-rich domain comprising residues 139 to 184 has remained elusive. To resolve the function of the RafC1 domain, we have performed an exhaustive surface scanning mutagenesis. In our study, we defined a high-resolution map of multiple distinct functional epitopes within RafC1 that are required for both negative control of the kinase and the positive function of the protein. Activating mutations in three different epitopes enhanced Ras-dependent Raf activation, while only some of these mutations markedly increased Raf basal activity. One contiguous inhibitory epitope consisting of S177, T182, and M183 clearly contributed to Ras-Raf binding energy and represents the putative Ras binding site of the RafC1 domain. The effects of all RafC1 mutations on Ras binding and Raf activation were independent of Ras lipid modification. The inhibitory mutation L160A is localized to a position analogous to the phorbol ester binding site in the protein kinase C C1 domain, suggesting a function in cofactor binding. Complete inhibition of Ras-dependent Raf activation was achieved by combining mutations K144A and L160A, which clearly demonstrates an absolute requirement for correct RafC1 function in Ras-dependent Raf activation.

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