scholarly journals Structure of the human marker of self 5-transmembrane receptor CD47

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gustavo Fenalti ◽  
Nicolas Villanueva ◽  
Mark Griffith ◽  
Barbra Pagarigan ◽  
Sirish Kaushik Lakkaraju ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Recognition ◽  
Blocking Antibody ◽  
Loop Region ◽  
Macrophage Phagocytosis ◽  
Hydrogen Deuterium ◽  
A Cell ◽  
Tm Domain ◽  
Dynamics Simulations

AbstractCD47 is the only 5-transmembrane (5-TM) spanning receptor of the immune system. Its extracellular domain (ECD) is a cell surface marker of self that binds SIRPα and inhibits macrophage phagocytosis, and cancer immuno-therapy approaches in clinical trials are focused on blocking CD47/SIRPα interaction. We present the crystal structure of full length CD47 bound to the function-blocking antibody B6H12. CD47 ECD is tethered to the TM domain via a six-residue peptide linker (114RVVSWF119) that forms an extended loop (SWF loop), with the fundamental role of inserting the side chains of W118 and F119 into the core of CD47 extracellular loop region (ECLR). Using hydrogen-deuterium exchange and molecular dynamics simulations we show that CD47’s ECLR architecture, comprised of two extracellular loops and the SWF loop, creates a molecular environment stabilizing the ECD for presentation on the cell surface. These findings provide insights into CD47 immune recognition, signaling and therapeutic intervention.

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Cheng-Hsiang Kuo ◽  
Po-Ku Chen ◽  
Bi-Ing Chang ◽  
Meng-Chen Sung ◽  
Chung-Sheng Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Egf Receptor ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
A Cell ◽  
Lewis Y ◽  
Tm Domain

AbstractLewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube formation on Matrigel. Blockade of LeY with rTMD1 or Ab against LeY inhibited endothelial tube formation in vitro. Epidermal growth factor (EGF) receptor in HUVECs was LeY modified. rTMD1 inhibited EGF receptor signaling, chemotaxis, and tube formation in vitro, and EGF-mediated angiogenesis and tumor angiogenesis in vivo. We concluded that LeY is involved in vascular endothelial tube formation and rTMD1 inhibits angiogenesis via interaction with LeY. Administration of rTMD1 or recombinant adeno-associated virus vector carrying TMD1 could be a promising antiangiogenesis strategy.

scholarly journals Neisseria gonorrhoeae Porin P1.B Induces Endosome Exocytosis and a Redistribution of Lamp1 to the Plasma Membrane

2002 ◽  
Vol 70 (11) ◽  
pp. 5965-5971 ◽  
Author(s):  
Patricia Ayala ◽  
Brandi Vasquez ◽  
Lee Wetzler ◽  
Magdalene So
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Neisseria Gonorrhoeae ◽  
Bacterial Infection ◽  
Immunoglobulin A ◽  
Late Endosomes ◽  
A Cell ◽  
Iga Protease

ABSTRACT The immunoglobulin A (IgA) protease secreted by pathogenic Neisseria spp. cleaves Lamp1, thereby altering lysosomes in a cell and promoting bacterial intracellular survival. We sought to determine how the IgA protease gains access to cellular Lamp1 in order to better understand the role of this cleavage event in bacterial infection. In a previous report, we demonstrated that the pilus-induced Ca2+ transient triggers lysosome exocytosis in human epithelial cells. This, in turn, increases the level of Lamp1 at the plasma membrane, where it can be cleaved by IgA protease. Here, we show that porin also induces a Ca2+ flux in epithelial cells. This transient is similar in nature to that observed in phagocytes exposed to porin. In contrast to the pilus-induced Ca2+ transient, the porin-induced event does not trigger lysosome exocytosis. Instead, it stimulates exocytosis of early and late endosomes and increases Lamp1 on the cell surface. These results indicate that Neisseria pili and porin perturb Lamp1 trafficking in epithelial cells by triggering separate and distinct Ca2+-dependent exocytic events, bringing Lamp1 to the cell surface, where it can be cleaved by IgA protease.

scholarly journals Genetic Characterization of a Cell Envelope-Associated Proteinase from Lactobacillus helveticus CNRZ32

1999 ◽  
Vol 181 (15) ◽  
pp. 4592-4597 ◽  
Author(s):  
Jeffrey A. Pederson ◽  
Gerald J. Mileski ◽  
Bart C. Weimer ◽  
James L. Steele
Keyword(s):  
Cell Surface ◽  
Deletion Mutant ◽  
Cell Envelope ◽  
Physiological Role ◽  
Lactobacillus Helveticus ◽  
Whole Cells ◽  
A Cell ◽  
Hydrolysis Of

ABSTRACT A cell envelope-associated proteinase gene (prtH) was identified in Lactobacillus helveticus CNRZ32. TheprtH gene encodes a protein of 1,849 amino acids and with a predicted molecular mass of 204 kDa. The deduced amino acid sequence of the prtH product has significant identity (45%) to that of the lactococcal PrtP proteinases. Southern blot analysis indicates thatprtH is not broadly distributed within L. helveticus. A prtH deletion mutant of CNRZ32 was constructed to evaluate the physiological role of PrtH. PrtH is not required for rapid growth or fast acid production in milk by CNRZ32. Cell surface proteinase activity and specificity were determined by hydrolysis of αs1-casein fragment 1-23 by whole cells. A comparison of CNRZ32 and its prtH deletion mutant indicates that CNRZ32 has at least two cell surface proteinases that differ in substrate specificity.

Phyllotaxis Turns over a New Leaf – A Review

2019 ◽  
Author(s):  
Derek T Lamport ◽  
Li Tan ◽  
Michael Held ◽  
Marcia Kieliszewski
Keyword(s):  
Cell Surface ◽  
Calcium Binding ◽  
Wall Stress ◽  
Protein Chemistry ◽  
Computer Prediction ◽  
Cell Wall Stress ◽  
A Cell ◽  
Ancient Problem ◽  
General Explanation

Sixty years ago in the lab adjacent to Fred Sanger (1958 Nobel Prize for protein chemistry), I discovered the cell surface hydroxyproline-rich glycoproteins. Nature keeps some of her secrets longer than others. It has taken many years to dissect the molecular function and biological role of extensins and arabinogalactan proteins (AGPs). Extensins template the formation of new cell walls. AGPs remained baffling and enigmatic until a Eureka moment when computer prediction of AGP calcium binding depicted paired glucuronic acid residues and thus the likely role of a cell surface AGP-Ca2+capacitor: In conjunction with the auxin-activated proton pump that releases bound Ca2+ it led us to formulate the Hechtian Growth Oscillator as A Global Paradigm with a pivotal role in Ca2+ homeostasis. The ramifications are profound. They cannot be shrugged off with sceptical disdain but demand critical reappraisal of current dogma. Phyllotaxis is an ancient problem; it involves an essential role for auxin and the auxin efflux “PIN” proteins together with mechanotransduction of stress-strain as phyllotactic determinants. However, a general explanation remains elusive despite much effort, particularly by mathematicians. Here we propose a novel biochemical algorithm: Hechtian oscillator transduction of cell wall stress generates phyllotactic patterns quite independent of a mathematical approach. Plants simply use different rules and follow a different route.

Fcγ receptor transmembrane domains: role in cell surface expression, γ chain interaction, and phagocytosis

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4479-4484 ◽  
Author(s):  
Moo-Kyung Kim ◽  
Zhen-Yu Huang ◽  
Pyoung-Han Hwang ◽  
Brian A. Jones ◽  
Norihito Sato ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Fcγ Receptors ◽  
Chimeric Receptors ◽  
Chain Dimer ◽  
Tm Domain ◽  
Chain Interaction ◽  
Specific Sequences

Abstract We constructed chimeric receptors to dissect the role of the transmembrane (TM) domain in cell surface expression of and phagocytosis by the γ chain–dependent Fcγ receptors FcγRIIIA and FcγRI. FcγR chimeras containing the TM and cytoplasmic (CY) domains of the γ chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcγRIIIA TM were poorly expressed. Receptors containing the FcγRI TM and the γ chain CY but lacking the γ chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a γ chain dimer induced by the γ chain TM is not required for efficient phagocytosis. Cotransfection of FcγRI or FcγRIIIA with the chimera CD8-γ-γ (EC-TM-CY) resulted in FcγR cell surface expression and phagocytosis, whereas CD8-CD8-γ, whose TM does not associate with FcγR, allowed cell surface expression of (but not phagocytosis by) FcγRI. CD8-CD8-γ also did not allow surface expression of FcγRIIIA. Exchanging FcγRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcγRI TM are essential for association of FcγRI with the γ chain and phagocytosis. The data indicate that specific sequences in the FcγRIIIA and FcγRI TMs govern their different interactions with the γ chain in cell surface expression and phagocytosis and that γ chain TM sequences are not required for γ chain–mediated phagocytosis. The data identify a specific region of the FcγRI TM and its asparagine as important for FcγRI cell surface expression in the absence of the γ chain and for distinguishing the FcγRI and FcγRIIIA phenotypes.

scholarly journals Teratocarcinoma stem cell adhesion: the role of divalent cations and a cell surface lectin.

1983 ◽  
Vol 96 (6) ◽  
pp. 1532-1537 ◽  
Author(s):  
L B Grabel ◽  
M S Singer ◽  
G R Martin ◽  
S D Rosen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Divalent Cations ◽  
Intercellular Adhesion ◽  
The Other ◽  
Calcium Dependent ◽  
A Cell

We describe two additive systems of intercellular adhesion in teratocarcinoma stem cells (Nulli cell line). One component is divalent cation-dependent (Ca++ or Mg++) and the other involves a cell surface fucan/mannan-specific lectin, previously identified on stem cells by an erythrocyte rosetting assay. The existence of these two systems is inferred from the observation that reaggregation of stem cells was partially inhibited by the removal of divalent cations or by the presence of lectin inhibitors such as fucoidan, but reaggregation was completely blocked when the two conditions were combined. Our results are related to recent work describing a calcium-dependent system of intercellular adhesion in teratocarcinoma stem cells.

scholarly journals Replacement of the phospholipid-anchor in the contact site A glycoprotein of D. discoideum by a transmembrane region does not impede cell adhesion but reduces residence time on the cell surface

1994 ◽  
Vol 124 (1) ◽  
pp. 205-215 ◽  
Author(s):  
A Barth ◽  
A Müller-Taubenberger ◽  
P Taranto ◽  
G Gerisch
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Transmembrane Region ◽  
Contact Site ◽  
A Cell ◽  
Internalization Rate ◽  
Actin Promoter ◽  
Wild Type Form

The contact site A (csA) glycoprotein of Dictyostelium discoideum, a cell adhesion molecule expressed in aggregating cells, is inserted into the plasma membrane by a ceramide-based phospholipid (PL) anchor. A carboxyterminal sequence of 25 amino acids of the primary csA translation product proved to contain the signal required for PL modification. CsA is known to be responsible for rapid, EDTA-resistant cohesion of cells in agitated suspensions. To investigate the role of the PL modification of this protein, the anchor was replaced by the transmembrane region and short cytoplasmic tail of another plasma membrane protein of D. discoideum. In cells transformed with appropriate vectors, PL-anchored or transmembrane csA was expressed under the control of an actin promoter during growth and development. The transmembrane form enabled the cells to agglutinate in the presence of shear forces, similar to the PL-anchored wild-type form. However, the transmembrane form was much more rapidly internalized and degraded. In comparison to other cell-surface glycoproteins of D. discoideum the internalization rate of the PL-anchored csA was extremely slow, most likely because of its exclusion from the clathrin-mediated pathway of pinocytosis. Thus, our results indicate that the phospholipid modification is not essential for the csA-mediated fast type of cell adhesion but guarantees long persistence of the protein on the cell surface.

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