Theoretical study on mutation-induced activation of the luteinizing hormone receptor.
Here, three-dimensional model building and molecular dynamics simulations of the luteinizing hormone receptor have been employed to generate hypotheses about the molecular mechanisms underlying the activation of the receptor induced by naturally occurring activating mutations. The comparative analysis of the wild-type receptor and of 16 constitutively active or inactive mutants has been instrumental in inferring the structural/dynamic features which could characterize the inactive and the active forms of the receptor. These features have been also employed for predicting the functional behavior of new receptor mutants. The results of this study might provide a structural framework to interpret the pathological effects induced by mutations of the luteinizing hormone receptor. In addition, the proposed theoretical model could be useful for engineering new mutations or ligands able to modulate receptor function.
Fanelli
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Dipartimento di Chimica, Universita di Modena e Reggio Emilia, Via Campi 183, Modena, 41100, Italy. fanelli@unimo.it
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003198:Computer Simulation; D017124:Conserved Sequence; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011487:Protein Conformation; D015202:Protein Engineering; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism; D011974:Receptors, LH / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
C547716:ADRA1B protein, human; D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1; D011974:Receptors, LH