Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site.

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Abstract Text:

The C terminus is responsible for all of the agonist activity of C5a at human C5a receptors (C5aRs). In this report we have mapped the ligand binding site on the C5aR using a series of agonist and antagonist peptide mimics of the C terminus of C5a as well as receptors mutated at putative interaction sites (Ile(116), Arg(175,) Arg(206), Glu(199), Asp(282), and Val(286)). Agonist peptide 1 (Phe-Lys-Pro-d-cyclohexylalanine-cyclohexylalanine-d-Arg) can be converted to an antagonist by substituting the bulkier Trp for cyclohexylalanine at position 5 (peptide 2). Conversely, mutation of C5aR transmembrane residue Ile(116) to the smaller Ala (I116A) makes the receptor respond to peptide 2 as an agonist (Gerber, B. O., Meng, E. C., Dotsch, V., Baranski, T. J., and Bourne, H. R. (2001) J. Biol. Chem. 276, 3394-3400). However, a potent cyclic hexapeptide antagonist, Phe-cyclo-[Orn-Pro-d-cyclohexylalanine-Trp-Arg] (peptide 3), derived from peptide 2 and which binds to the same receptor site, remains a full antagonist at I116AC5aR. This suggests that although the residue at position 5 might bind near to Ile(116), the latter is not essential for either activation or antagonism. Arg(206) and Arg(175) both appear to interact with the C-terminal carboxylate of C5a agonist peptides, suggesting a dynamic binding mechanism that may be a part of a receptor activation switch. Asp(282) has been previously shown to interact with the side chain of the C-terminal Arg residue, and Glu(199) may also interact with this side chain in both C5a and peptide mimics. Using these interactions to orient NMR-derived ligand structures in the binding site of C5aR, a new model of the interaction between peptide antagonists and the C5aR is presented.

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Publishing Authors By Initials

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 280

Page Numbers: 17831-40

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 20

MONTH: 01

YEAR: 2005

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Keywords Mesh Terms:

KEYWORDS: Receptors, Complement

MESH TERMS: metabolism

Chemical & Substance for Abstract: Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. Information

Substance Name: Receptors, Complement

Registry Number: 0

Grant and Affiliation Information for Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site.

AFFILIATION: Academic Neurology Unit, University of Sheffield Medical School, Sheffield S10 2RX, United Kingdom.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site Related Publications

• A Visual Analogue Scale technique to measure global vigor and affect.
• A curious eruption: erythema gyratum repens in resolving pustular psoriasis.
• Age wise: aging well by sleeping well.
• An efficient screening tool for preoperative depression: the geriatric depression scale-short form.
• Candida albicans drug resistance another way to cope with stress.
• Cervical neoplasia in pregnancy. Part 2: current treatment of invasive disease.
• Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site.
• Conference report for the 2(nd) MC-GARD series on "Interplay among genetics, epigenetics and non-coding RNAs".
• Cost-effectiveness of adding human papilloma virus testing to a managed care cervical cancer screening program.
• Effects of mothers' prenatal psychiatric status and postnatal caregiving on infant biobehavioral regulation: Can prenatal programming be modified?
• Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network.
• Influence of crystalloid and colloid replacement solutions on hemodynamic variables during acute normovolemic hemodilution.
• Injuries of the tibio-fibular ligaments.
• Personality correlates with sleep-wake variables.
• Practical consequences of fatigue-related performance failures.
• Pregnant women's cortisol is elevated with anxiety and depression - but only when comorbid.
• Prenatal predictors of infant temperament.
• Radiographic technique chart.
• Recognition of facial emotions among maltreated children with high rates of post-traumatic stress disorder.
• Regulative feedback in pattern formation: towards a general relativistic theory of positional information.
• Relationship between trait anxiety, prefrontal cortex, and attention bias to angry faces in children and adolescents.
• Single-cell analysis of unstable genes.
• Stress, immunity, and cervical cancer: biobehavioral outcomes of a randomized clinical trail.
• The Pediatrician's Role in Preventing Cervical Cancer.
• The construction of cDNA libraries from human single preimplantation embryos and their use in the study of gene expression during development.
• The flowering of systems approaches in plant and crop biology.
• The lingering death of the autopsy.
• Topical fluorouracil in vitiligo.
• Traumatic ischaemia of the calf.
• Type and severity of cognitive decline in older adults after noncardiac surgery.