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NIH Research Festival

September 14 – 16, 2016

Significance of a Tripeptide Motif- Leu-Tyr-Arg (LYR) Fe-S Cluster Acquisition by Proteins

Thursday, September 15, 2016 – Poster Session III
3:30 – 5:00 p.m.

FAES Terrace

NICHD

MOLBIO-21

Authors

  • A Jain
  • A Singh
  • N Maio
  • TA Rouault

Abstract

Fe-S cluster biogenesis is a well elucidated pathway. Recently, a co-chaperone, HSC20 (exclusively involved in Fe-S cluster pathway) was discovered, which accepts electrons from the Fe-S cluster scaffold protein, ISCU and transfers it to the recipient protein, SDHB. HSC20, recognizes a tripeptide motif, Leu-Tyr-Arg (LYR) on SDHB and transfers the cluster to the target. This study provides an important insight into the Fe-S acquisition clusters by recipient proteins. Based on this study, we hypothesized that the presence of LYR motif serves as a recognition site for HSC20 and this interaction allows the delivery of Fe-S cluster from the co-chaperone to the target protein. In this study, we identified approximately 1000 proteins in human proteome containing the LYR-tripeptide motif and four cysteine residues to house the cofactor. The study was initiated with the series of proteins involved in kidney cancer (PTEN, mTOR, CUL2, TSC1). Our results from co-immunoprecipitation and yeast-two-hybrid assays suggest a positive interaction between HSC20 and these proteins. Subsequently, these proteins were anaerobically purified from E.coli; and currently, are being investigated for the presence of Fe-S clusters using spectrophotometric and radioactive assays. Identification of Fe-S clusters in these proteins will yield new mechanistic insight into the signal transduction cascades and divulge a novel signaling molecule in cellular biochemistry. Further on, a structural analysis on the purified proteins and the binding pocket will enable us to extrapolate and simulate of the features of unknown Fe-S containing protein.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Friday, March 26, 2021

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Download the 2016 Research Festival Schedule Overview (6 pages)

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