Guo-Ping Zhou
Gordon Life Science Institute, Boston, USA
Title: The NMR Studies of the Interaction between Polysialic Acid (polySA) and the PSTD Peptide in ST8Sia IV Polysialytranseferase
Biography
Biography: Guo-Ping Zhou
Abstract
The α2,8-sialyltransferase (ST8Sia) family consists of 6 sia-lytranseferases, which are related to forms of polysialic acid chains (PSA) on neural cell adhesion molecule (NCAM) and NCAM polysialylation, and have important effects on formation of sialic acid storage diseases, neural system diseases and invasive cancers. It has been known that synthesis of PSA chains is catalysed by two polysialyltransferases, ST8Sia II (STX) and ST8Sia IV (PST). In addition, a polybasic motif of 32 amino acids in both ST8Sia II and ST8Sia IV has been designated as “polysialytransferase domain” (PSTD), which is essential for NCAM polysialylation. In this study, we have determined the 3D structure of the PSTD peptide containing 22 amino acids (22AA) in ST8Sia IV using NMR spectroscopy. This NMR-based model displays that the PSTD domain consists of an α-helical segment, two unstructured domains in both N- and C-terminus, and two three-residue-loops near the C-terminus of the peptide. Our overlaid 2D 1H-15N-HSQC spectra of the 22AA-PSTD peptide show that the amide proton chemical shifts of some amino acids such as I260, I261, H262, R265, L269 and K272 have been changed after polySA was mixed with the PSTD peptide. In addition, the peak intensity of A263, V264, R265, Y267, L269 and K272 were also decreased after adding polySA. However, there is no any change in both chemical shift and the amide proton peak intensity for all other residues located on outside of the helix. Above NMR results indicate a weak interaction exists between the helix of the PSTD and the PolySA, which may play a vital roles in modulating biosynthesis of polySA chain and NCAM polysialylation.
References:
- Huang RB, Cheng D, Lu B, Liao SM Troy li, FA, Zhou GP (2017) The Intrinsic Relationship between Structure and Function of the Sialytransferase ST8Sia Family Members. Curr. Top. Med. Chem. 7(21):2359-2369.
- Zhou G P, W Z Zhong (2016). Perspectives in the medicinal chemistry. Current Topics in Medicinal Chemistry.16(4):381-382.
- Zhou G P (2016) Modulations and their biological functions of protein-biomolecule interactions. Current Topics in Medicinal Chemistry. 16(6):579-580.
- Zhou G P, Chen D, Liao S, Huang R B (2016) Recent progresses in studying helix-helix interactions in proteins by incorporating the Wenxiang diagram into the NMR spectroscopy. Current Topics in Medicinal Chemistry, 16(6)581-590.
- Zhou G P, Huang R B, Troy, F A (2015) 3D Structural Con formation and Functional Domains of Polysialyltransferase ST8Sia IV Required for Polysialylation of Neural Cell Adhesion Molecules. Protein Peptide Lett. 22(2):137-148.