Platelet receptor recognition site on human fibrinogen. Synthesis and structure-function relationship of peptides corresponding to the carboxy-terminal segment of the .gamma. chain

Biochemistry ◽  
1984 ◽  
Vol 23 (8) ◽  
pp. 1767-1774 ◽  
Author(s):  
Marek Kloczewiak ◽  
Sheila Timmons ◽  
Thomas J. Lukas ◽  
Jacek Hawiger
Keyword(s):  
Structure Function ◽  
Terminal Segment ◽  
Recognition Site ◽  
Gamma Chain ◽  
Human Fibrinogen ◽  
Platelet Receptor ◽  
Receptor Recognition ◽  
Function Relationship ◽  
Carboxy Terminal ◽  
Relationship Of

Platelet receptor recognition domains on the .alpha. chain of human fibrinogen: structure-function analysis

Biochemistry ◽  
1989 ◽  
Vol 28 (7) ◽  
pp. 2909-2914 ◽  
Author(s):  
Jacek Hawiger ◽  
Marek Kloczewiak ◽  
Maria A. Bednarek ◽  
Sheila Timmons
Keyword(s):  
Structure Function ◽  
Function Analysis ◽  
Human Fibrinogen ◽  
Alpha Chain ◽  
Platelet Receptor ◽  
Receptor Recognition

Platelet receptor recognition domain on the .gamma. chain of human fibrinogen and its synthetic peptide analogues

Biochemistry ◽  
1989 ◽  
Vol 28 (7) ◽  
pp. 2915-2919 ◽  
Author(s):  
Marek Kloczewiak ◽  
Sheila Timmons ◽  
Maria A. Bednarek ◽  
Masato Sakon ◽  
Jacek Hawiger
Keyword(s):  
Synthetic Peptide ◽  
Gamma Chain ◽  
Human Fibrinogen ◽  
Platelet Receptor ◽  
Receptor Recognition ◽  
Peptide Analogues

Platelet receptor recognition domain on the .gamma. chain of human fibrinogen and its synthetic peptide analogs [Erratum to document cited in CA110(17):151810E]

Biochemistry ◽  
1989 ◽  
Vol 28 (19) ◽  
pp. 7974-7974
Author(s):  
Marek Kloczewiak ◽  
Sheila Timmons ◽  
Maria A. Bednarek ◽  
Masato Sakon ◽  
Jacek Hawiger
Keyword(s):  
Synthetic Peptide ◽  
Gamma Chain ◽  
Human Fibrinogen ◽  
Peptide Analogs ◽  
Platelet Receptor ◽  
Receptor Recognition

Role of aromatic residues in the structure-function relationship of .alpha.-bungarotoxin

Biochemistry ◽  
1982 ◽  
Vol 21 (11) ◽  
pp. 2592-2600 ◽  
Author(s):  
Yee Hsiung Chen ◽  
Jang Chyi Tai ◽  
Wan Jen Huang ◽  
Ming Zong Lai ◽  
Mien Chie Hung ◽  
...  
Keyword(s):  
Structure Function ◽  
Aromatic Residues ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Alpha Bungarotoxin ◽  
Relationship Of

Gene cloning and structure - function relationship of cytokines such as TNF and interleukins

1987 ◽  
Vol 16 (3-4) ◽  
pp. 219-226 ◽  
Author(s):  
Walter Fiers ◽  
Rudi Beyaert ◽  
Peter Brouckaert ◽  
Bart Everaerdt ◽  
Guy Haegeman ◽  
...  
Keyword(s):  
Structure Function ◽  
Gene Cloning ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Relationship Of

scholarly journals Pleiotropic functions of the transmembrane domain 6 of human melanocortin-4 receptor

2012 ◽  
Vol 49 (3) ◽  
pp. 237-248 ◽  
Author(s):  
Hui Huang ◽  
Ya-Xiong Tao
Keyword(s):  
Cell Surface ◽  
Structure Function ◽  
Transmembrane Domain ◽  
Mapk Pathway ◽  
Surface Expression ◽  
Camp Signaling ◽  
Cell Surface Expression ◽  
Melanocortin 4 Receptor ◽  
Function Relationship ◽  
Relationship Of

The melanocortin-4 receptor (MC4R) is a critical regulator of energy homeostasis and has emerged as a premier target for obesity treatment. Numerous mutations in transmembrane domain 6 (TM6) of MC4R resulting in functional alterations have been identified in obese patients. Several mutagenesis studies also provided some data suggesting the importance of this domain in receptor function. To gain a better understanding of the structure–function relationship of the receptor, we performed alanine-scanning mutagenesis in TM6 to determine the functions of side chains. Of the 31 residues, two were important for cell surface expression, five were indispensable for α-melanocyte-stimulating hormone (α-MSH) and β-MSH binding, and six were important for signaling in the Gs–cAMP–PKA pathway. H264A, targeted normally to the plasma membrane, was undetectable by competitive binding assay and severely defective in basal and stimulated cAMP production and ERK1/2 phosphorylation. Nine mutants had decreased basal cAMP signaling. Seven mutants were constitutively active in cAMP signaling and their basal activities could be inhibited by two MC4R inverse agonists, Ipsen 5i and ML00253764. Five mutants were also constitutively active in the MAPK pathway with enhanced basal ERK1/2 phosphorylation. In summary, our study provided comprehensive data on the structure–function relationship of the TM6 of MC4R. We identified residues that are important for cell surface expression, ligand binding, cAMP generation, and residues for maintaining the WT receptor in active conformation. We also reported constitutive activation of the MAPK pathway and biased signaling. These data will be useful for rationally designing MC4R agonists and antagonists for treatment of eating disorders.

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