Structure-function correlations of the insulin-linked polymorphic region

Journal of Molecular Biology
P CatastiG Gupta

Abstract

The insulin minisatellite of the insulin-linked polymorphic region (ILPR), a 14 base-pairs long tandem repeat of: 5'-ACAGGGGTGTGGGG-3' 3'-TGTCCCCACACCCC-5', is located 363 base-pairs upstream of the human insulin gene. A locus for insulin-dependent diabetes mellitus (IDDM) has been mapped to the ILPR. It has been shown that the ILPR is polymorphic in length and this length polymorphism is also related to the transcriptional activity of the insulin gene and the susceptibility to IDDM. Here, we attempt to decipher the role of the ILPR structure in length polymorphism and transcriptional regulation. We show by gel electrophoresis, circular dichroism (CD) and one and two-dimensional nuclear magnetic resonance spectroscopy (1D/2D NMR) that the G-rich strand of the ILPR adopts an intramolecularly folded hairpin G-quartet structure. A detailed analysis of 1D/2D NMR data of d(G4TGTG4) and d(G4TGTG4ACAG4TGTG4) enables us to define the nature of chainfolding, the stacking interaction of the G-tetrads in the stem, and the interactions of the bases in the loops. d(G4TGTG4ACAG4TGTG4) happens to be the smallest unit of the G-rich strand that can form the intramolecular hairpin G-quartet structure. For long ILPR sequences, several such hairpi...Continue Reading

Citations

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