| Title | Single-nucleotide polymorphism of PPARγ, a protein at the crossroads of physiological and pathological processes |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2017 |
| Authors | Petrosino, M., Lori L., Pasquo A., Lori C., Consalvi V., Minicozzi V., Morante S., Laghezza A., Giorgi A., Capelli D., and Chiaraluce R. |
| Journal | International Journal of Molecular Sciences |
| Volume | 18 |
| ISSN | 16616596 |
| Keywords | Amino Acid Sequence, amino acid substitution, article, binding site, Binding Sites, carcinogenesis, cell differentiation, chemistry, circular dichroism, controlled study, DNA transcription, drug effects, fast protein liquid chromatography, gel filtration chromatography, gene, Gene expression, Genetic, genetic transcription, Genetic variability, genetics, human, human cell, Humans, insulin resistance, ligand, Ligands, lipid metabolism, lipodystrophy, matrix assisted laser desorption ionization time of flight mass spectrometry, metabolism, molecular dynamics, Molecular dynamics simulation, peroxisome proliferator activated receptor gamma, peroxisome proliferator activated receptor gamma gene, Polymorphism, PPAR gamma, protein binding, Protein Conformation, protein domain, protein expression, Protein Interaction Domains and Motifs, protein purification, protein unfolding, Single Nucleotide, single nucleotide polymorphism, structure activity relation, Structure-Activity Relationship, thermodynamics, thermostability, Transcription, Urea |
| Abstract | Genome polymorphisms are responsible for phenotypic differences between humans and for individual susceptibility to genetic diseases and therapeutic responses. Non-synonymous single-nucleotide polymorphisms (nsSNPs) lead to protein variants with a change in the amino acid sequence that may affect the structure and/or function of the protein and may be utilized as efficient structural and functional markers of association to complex diseases. This study is focused on nsSNP variants of the ligand binding domain of PPARγ a nuclear receptor in the superfamily of ligand inducible transcription factors that play an important role in regulating lipid metabolism and in several processes ranging from cellular differentiation and development to carcinogenesis. Here we selected nine nsSNPs variants of the PPARγ ligand binding domain, V290M, R357A, R397C, F360L, P467L, Q286P, R288H, E324K, and E460K, expressed in cancer tissues and/or associated with partial lipodystrophy and insulin resistance. The effects of a single amino acid change on the thermodynamic stability of PPARγ, its spectral properties, and molecular dynamics have been investigated. The nsSNPs PPARγ variants show alteration of dynamics and tertiary contacts that impair the correct reciprocal positioning of helices 3 and 12, crucially important for PPARγ functioning. © 2017 by the authors; licensee MDPI, Basel, Switzerland. |
| Notes | cited By 1 |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85012203027&doi=10.3390%2fijms18020361&partnerID=40&md5=88e43307a8953f017345f7f44a276e78 |
| DOI | 10.3390/ijms18020361 |
| Citation Key | Petrosino2017 |
