Ligand Binding Results in Divalent Cation Displacement from the α2β1Integrin I Domain:  Evidence from Terbium Luminescence Spectroscopy†

Biochemistry ◽  
1998 ◽  
Vol 37 (32) ◽  
pp. 11280-11288 ◽  
Author(s):  
S. Kent Dickeson ◽  
Maitrayee Bhattacharyya-Pakrasi ◽  
Nancy L. Mathis ◽  
Paul H. Schlesinger ◽  
Samuel A. Santoro
Keyword(s):  
Ligand Binding ◽  
Divalent Cation ◽  
Luminescence Spectroscopy ◽  
Terbium Luminescence

A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation

Science ◽  
1990 ◽  
Vol 249 (4971) ◽  
pp. 915-918 ◽  
Author(s):  
J. Loftus ◽  
T. O'Toole ◽  
E. Plow ◽  
A Glass ◽  
A. Frelinger ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Divalent Cation

scholarly journals Divalent cation regulation of the function of the leukocyte integrin LFA-1.

1992 ◽  
Vol 116 (1) ◽  
pp. 219-226 ◽  
Author(s):  
I Dransfield ◽  
C Cabañas ◽  
A Craig ◽  
N Hogg
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
Divalent Cation ◽  
Functional Activity ◽  
Function Analysis ◽  
Divalent Cations ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Cell Binding ◽  
Intercellular Adhesion Molecule 1

The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte integrin functional activity. We have assessed the role of divalent cations Mg2+, Ca2+, and Mn2+ in LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) and induction of the divalent cation-dependent epitope recognized by mAb 24. Manganese strongly promoted both expression of the 24 epitope and T cell binding to ICAM-1 via LFA-1, suggesting that Mn2+ is able to directly alter the conformation of LFA-1 in a manner that favors ligand binding. Since Mn2+ also promotes functional activity of other integrins, parallels in mechanism of ligand binding may span the integrin family. In contrast, induction of 24 epitope expression by Mg2+ required removal of Ca2+ from T cell LFA-1 with EGTA. Furthermore, binding of mAb 24 to T cell LFA-1 in the presence of either Mn2+ or Mg2+ was found to be specifically inhibited by Ca2+, suggestive of a negative regulatory role for Ca2+ in the control of leukocyte integrin function. Analysis of T cell binding to ICAM-1 via LFA-1 in the presence of Mg2+ or Mn2+, confirmed that Ca2+ exerted inhibitory effects upon LFA-1 function. The implication of our findings is that Ca2+ bound with relatively high affinity to LFA-1 may serve to maintain an inactive state. Thus induction of function and 24 epitope expression may occur as a result of displacement of Ca2+ from leukocyte integrins or alternatively, such activators may be able to impose the required conformational change in the presence of bound Ca2+.

CarR, a MarR-family regulator from Corynebacterium glutamicum, modulated antibiotic and aromatic compound resistance

2019 ◽  
Vol 476 (21) ◽  
pp. 3141-3159 ◽  
Author(s):  
Meiru Si ◽  
Can Chen ◽  
Zengfan Wei ◽  
Zhijin Gong ◽  
GuiZhi Li ◽  
...  
Keyword(s):  
Stress Response ◽  
Ligand Binding ◽  
Corynebacterium Glutamicum ◽  
Conformational Changes ◽  
Cysteine Oxidation ◽  
Transcriptional Regulatory ◽  
Ligand Free ◽  
Redox Sensing

Abstract MarR (multiple antibiotic resistance regulator) proteins are a family of transcriptional regulators that is prevalent in Corynebacterium glutamicum. Understanding the physiological and biochemical function of MarR homologs in C. glutamicum has focused on cysteine oxidation-based redox-sensing and substrate metabolism-involving regulators. In this study, we characterized the stress-related ligand-binding functions of the C. glutamicum MarR-type regulator CarR (C. glutamicum antibiotic-responding regulator). We demonstrate that CarR negatively regulates the expression of the carR (ncgl2886)–uspA (ncgl2887) operon and the adjacent, oppositely oriented gene ncgl2885, encoding the hypothetical deacylase DecE. We also show that CarR directly activates transcription of the ncgl2882–ncgl2884 operon, encoding the peptidoglycan synthesis operon (PSO) located upstream of carR in the opposite orientation. The addition of stress-associated ligands such as penicillin and streptomycin induced carR, uspA, decE, and PSO expression in vivo, as well as attenuated binding of CarR to operator DNA in vitro. Importantly, stress response-induced up-regulation of carR, uspA, and PSO gene expression correlated with cell resistance to β-lactam antibiotics and aromatic compounds. Six highly conserved residues in CarR were found to strongly influence its ligand binding and transcriptional regulatory properties. Collectively, the results indicate that the ligand binding of CarR induces its dissociation from the carR–uspA promoter to derepress carR and uspA transcription. Ligand-free CarR also activates PSO expression, which in turn contributes to C. glutamicum stress resistance. The outcomes indicate that the stress response mechanism of CarR in C. glutamicum occurs via ligand-induced conformational changes to the protein, not via cysteine oxidation-based thiol modifications.

Demonstration of a direct interaction between a colonic divalent cation receptor and the basolateral Na−H exchanger

2001 ◽  
Vol 120 (5) ◽  
pp. A529-A530
Author(s):  
P GEIBEL ◽  
M OREILLY ◽  
H VIEWEGER ◽  
K SIEBERT ◽  
N OBREIN ◽  
...  
Keyword(s):  
Divalent Cation ◽  
Direct Interaction ◽  
Cation Receptor
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