Linked Life Data

8106386

Source:http://linkedlifedata.com/resource/pubmed/id/8106386

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-3-18
pubmed:abstractText
The N-formylated tripeptide, formylmethionylleucyl-phenylalanine (fMLP), and the 74-amino-acid long human C5a anaphylatoxin activate phagocytic cells via two structurally related G protein-coupled receptors (FPR and C5aR), which are 34% identical in amino acid sequence. C5aR chimeras were constructed in which the entire NH2-terminal extracellular sequence or part of it was replaced by the counterparts from FPR or FPRH. Although the NH2-terminal region of C5aR presents an extremely high interspecies variability, substitution of the entire NH2-terminal sequence of C5aR by that of FPR or FPRH surprisingly resulted in chimeras that were apparently retained in the endoplasmic reticulum. In contrast, when the NH2-terminal domain of FPR was replaced by the corresponding region from C5aR or FPRH normal expression to the plasma membrane and high affinity binding of N-formylated peptides were observed. Thus, the NH2-terminal region of C5aR, in contradistinction to that of FPR, seems to be required either for the translocation of C5aR through the ER membrane or for correct folding and sorting of C5aR to the plasma membrane. Replacement of the first 8 residues of C5aR by the corresponding region of FPR did not alter the cellular transport and the C5a binding capacity, whereas the exchange of the first 13 residues resulted in a chimera that was readily transported to the plasma membrane but showed no capability to bind C5a. Mutations of Asp into Asn in the NH2-terminal segment of C5aR further indicated that negative charges are required to endow the receptor with a C5a binding capacity. The residues critical for binding are either involved directly by interacting with cationic residues of C5a, or indirectly by influencing the overall structure of the ligand-binding site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3457-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8106386-Amino Acid Sequence, pubmed-meshheading:8106386-Animals, pubmed-meshheading:8106386-Base Sequence, pubmed-meshheading:8106386-Cell Line, pubmed-meshheading:8106386-Complement C5a, pubmed-meshheading:8106386-DNA Primers, pubmed-meshheading:8106386-Humans, pubmed-meshheading:8106386-Kinetics, pubmed-meshheading:8106386-Ligands, pubmed-meshheading:8106386-Molecular Sequence Data, pubmed-meshheading:8106386-Mutagenesis, Site-Directed, pubmed-meshheading:8106386-N-Formylmethionine Leucyl-Phenylalanine, pubmed-meshheading:8106386-Phosphorylation, pubmed-meshheading:8106386-Point Mutation, pubmed-meshheading:8106386-Polymerase Chain Reaction, pubmed-meshheading:8106386-Radioligand Assay, pubmed-meshheading:8106386-Receptor, Anaphylatoxin C5a, pubmed-meshheading:8106386-Receptors, Complement, pubmed-meshheading:8106386-Receptors, Formyl Peptide, pubmed-meshheading:8106386-Receptors, Immunologic, pubmed-meshheading:8106386-Receptors, Peptide, pubmed-meshheading:8106386-Recombinant Fusion Proteins, pubmed-meshheading:8106386-Restriction Mapping, pubmed-meshheading:8106386-Transfection
pubmed:year
1994
pubmed:articleTitle
The NH2-terminal region of C5aR but not that of FPR is critical for both protein transport and ligand binding.
pubmed:affiliation
Département de Biologie Moleculaire et Structurale/Laboratoire de Biochimie Centre National de la Recherche Scientifique, URA 1130, Centre d'Etudes Nucléaires, Grenoble, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't