scholarly journals Structural Model of MD-2 and Functional Role of Its Basic Amino Acid Clusters Involved in Cellular Lipopolysaccharide Recognition

2004 ◽  
Vol 279 (27) ◽  
pp. 28475-28482 ◽  
Author(s):  
Anton Gruber ◽  
Mateja Manček ◽  
Hermann Wagner ◽  
Carsten J. Kirschning ◽  
Roman Jerala
Keyword(s):  
Amino Acid ◽  
Functional Role ◽  
Structural Model ◽  
Basic Amino Acid

scholarly journals Role of peptide substrate structure in the selective processing of peptide prohormones at basic amino acid pairs by endoproteases

FEBS Letters ◽  
1988 ◽  
Vol 234 (1) ◽  
pp. 149-152 ◽  
Author(s):  
Pablo Gluschankof ◽  
Sophie Gomez ◽  
Agnès Lepage ◽  
Christophe Créminon ◽  
Fred Nyberg ◽  
...  
Keyword(s):  
Amino Acid ◽  
Basic Amino Acid ◽  
Peptide Substrate ◽  
Substrate Structure ◽  
Selective Processing

scholarly journals Functional role of polar amino acid residues in Na+/H+ exchangers

2001 ◽  
Vol 357 (1) ◽  
pp. 1 ◽  
Author(s):  
Christine A. WIEBE ◽  
Emily R. DiBATTISTA ◽  
Larry FLIEGEL
Keyword(s):  
Amino Acid ◽  
Functional Role ◽  
Amino Acid Residues ◽  
Polar Amino Acid

scholarly journals Identification of a functionally critical GXXG motif and its relationship to the folate binding site of the proton-coupled folate transporter (PCFT-SLC46A1)

2012 ◽  
Vol 303 (6) ◽  
pp. C673-C681 ◽  
Author(s):  
Rongbao Zhao ◽  
Daniel Sanghoon Shin ◽  
Andras Fiser ◽  
I. David Goldman
Keyword(s):  
Functional Role ◽  
Autosomal Recessive ◽  
Structural Model ◽  
Transmembrane Domain ◽  
Autosomal Recessive Disorder ◽  
Binding Pocket ◽  
Loss Of Function ◽  
Substituted Cysteine Accessibility ◽  
Translocation Pathway

The proton-coupled folate transporter (PCFT) mediates intestinal folate absorption, and loss-of-function mutations in this gene result in the autosomal recessive disorder hereditary folate malabsorption. The current study, focused on a structure-functional analysis of this transporter, identified Gly-189 and Gly-192 (a GxxG motif) located in the fifth transmembrane domain as residues that could not be replaced with alanine without a loss of function. In contrast, function was preserved when Gly-56 and Gly-59 (the other conservative GXXG motif in human PCFT) were replaced with alanine. Similarly, Gly-93 and Gly-97, which constitute the only conserved GXXXG dimerization motif in human PCFT, tolerated alanine substitution. To explore the role of this region in folate binding, the residues around Gly-189 and Gly-192 were analyzed by the substituted cysteine accessibility method. Both I188C and M193C mutants were functional and were inhibited by membrane-impermeable sulfhydryl-reactive reagents; this could be prevented with PCFT substrate, but the protection was sustained at 0°C only for the I188C mutant, consistent with localization of Ile-188 in the PCFT folate binding pocket. The functional role of residues around Gly-189 and Gly-192 is consistent with a molecular structural model in which these two residues along with Ieu-188 are accessible to the PCFT aqueous translocation pathway.

The Functional Significance of Endocrine-immune Interactions in Health and Disease

2020 ◽  
Vol 21 (1) ◽  
pp. 52-65
Author(s):  
Sridhar Muthusami ◽  
Balasubramanian Vidya ◽  
Esaki M Shankar ◽  
Jamuna Vadivelu ◽  
Ilangovan Ramachandran ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Differentiation ◽  
Amino Acid ◽  
Functional Role ◽  
Immune Cell ◽  
Amino Acid Derivatives ◽  
Endocrine Glands ◽  
Immune Systems ◽  
Health And Disease

Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field.

scholarly journals Integrin αVβ6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1

2004 ◽  
Vol 165 (5) ◽  
pp. 723-734 ◽  
Author(s):  
Justin P. Annes ◽  
Yan Chen ◽  
John S. Munger ◽  
Daniel B. Rifkin
Keyword(s):  
Functional Role ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Basic Amino Acid ◽  
Potential Interaction ◽  
Specific Function ◽  
Integrin Αvβ6 ◽  
The Matrix ◽  
Hinge Domain

Transforming growth factor-βs (TGF-β) are secreted as inactive complexes containing the TGF-β, the TGF-β propeptide, also called the latency-associated protein (LAP), and the latent TGF-β binding protein (LTBP). Extracellular activation of this complex is a critical but incompletely understood step in TGF-β regulation. We have investigated the role of LTBP in modulating TGF-β generation by the integrin αVβ6. We show that even though αvβ6 recognizes an RGD on LAP, LTBP-1 is required for αVβ6-mediated latent TGF-β activation. The domains of LTBP-1 necessary for activation include the TGF-β propeptide-binding domain and a basic amino acid sequence (hinge domain) with ECM targeting properties. Our results demonstrate an LTBP-1 isoform-specific function in αVβ6-mediated latent TGF-β activation; LTBP-3 is unable to substitute for LTBP-1 in this assay. The results reveal a functional role for LTBP-1 in latent TGF-β activation and suggest that activation of specific latent complexes is regulated by distinct mechanisms that may be determined by the LTBP isoform and its potential interaction with the matrix.

scholarly journals Association Between the Rat Homologue of CO-029, a Metastasis-associated Tetraspanin Molecule and Consumption Coagulopathy

1998 ◽  
Vol 141 (1) ◽  
pp. 267-280 ◽  
Author(s):  
Christoph Claas ◽  
Simone Seiter ◽  
Andreas Claas ◽  
Larissa Savelyeva ◽  
Manfred Schwab ◽  
...  
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibody ◽  
Amino Acid ◽  
Functional Role ◽  
Human Tumor ◽  
Tumor Cell Line ◽  
Metastatic Potential ◽  
Massive Bleeding ◽  
Consumption Coagulopathy

Recently, we have described a panel of metastasis-associated antigens in the rat, i.e., of molecules expressed on metastasizing, but not on nonmetastasizing tumor lines. One of these molecules, recognized by the monoclonal antibody D6.1 and named accordingly D6.1A, was found to be abundantly expressed predominantly on mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned. Surprisingly, the gene product proved to interfere strongly with coagulation. The 1.182-kb cDNA codes for a 235–amino acid long molecule with a 74.2% homology in the nucleotide and a 70% homology in the amino acid sequence to CO-029, a human tumor-associated molecule. According to the distribution of hydrophobic and hydrophilic amino acids, D6.1A belongs to the tetraspanin superfamily. Western blotting of D6.1A-positive metastasizing tumor lines revealed that the D6.1A, like many tetraspanin molecules, is linked to further membrane molecules, one of which could be identified as α6β1 integrin. Transfection of a low-metastasizing tumor cell line with D6.1A cDNA resulted in increased metastatic potential and provided a clue as to the functional role of D6.1A. We noted massive bleeding around the metastases and, possibly as a consequence, local infarctions predominantly in the mesenteric region and all signs of a consumption coagulopathy. By application of the D6.1 antibody the coagulopathy was counterregulated, though not prevented. It has been known for many years that tumor growth and progression is frequently accompanied by thrombotic disorders. Our data suggest that the phenomenon could well be associated with the expression of tetraspanin molecules.

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