Single-nucleotide polymorphism of PPARγ, a protein at the crossroads of physiological and pathological processes

Maria Petrosino, Laura Lori, Alessandra Pasquo, Clorinda Lori, Valerio Consalvi, Velia Minicozzi, Silvia Morante, Antonio Laghezza, Alessandra Giorgi, Davide Capelli, Roberta Chiaraluce

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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.
Original languageEnglish
Article number361
Pages (from-to)-
JournalInternational Journal of Molecular Sciences
Volume18
Issue number2
DOIs
Publication statusPublished - 10 Feb 2017
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Petrosino, M., Lori, L., Pasquo, A., Lori, C., Consalvi, V., Minicozzi, V., Morante, S., Laghezza, A., Giorgi, A., Capelli, D., & Chiaraluce, R. (2017). Single-nucleotide polymorphism of PPARγ, a protein at the crossroads of physiological and pathological processes. International Journal of Molecular Sciences, 18(2), -. [361]. https://doi.org/10.3390/ijms18020361