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Project Line 1: Lin12/ Notch Repeats (LNRs)

LNRs are highly conserved protein motifs of ~35 amino acids without substantial secondary structure or hydrophobic core.  They were first described as three unique tandem modules crucial for the regulation of ligand induced proteolytic cleavage of the Notch receptor.  Their correct folding requires the coordination of one Ca2+ ion by acidic amino acid residues and the formation of three specifically-paired disulfide bonds. (Figure 3)  

 

Studies under this project line have been designed to answer the following questions:

  • Is Ca2+ required for correct pattern of disulfide bond formation for all LNRs?

  • Can other divalent or trivalent metals direct correct disulfide bond formation?

  • Do LNRs bind any other divalent or trivalent metals once they are disulfide bonded?

  • Do all LNRs bind Ca2+  with similar affinities?

  • Does Ca2+ have any other role than aiding LNR folding?

  • Do the four and six cysteine containing LNRs form the same disulfide bonding pattern?

  • How does redox potential affect LNR folding?

  • How does the number of disulfide bonds affect the chemical stability?

  • How short can an LNR be?

Figure 3: NMR structure of human Notch LNRA (PDB ID: 1pb5 ) Vardar, D. et.al. Biochemistry.2003 Jun 17; 42(23):7061-7.

You can find the progress on each question in the poster presentations of our undergraduate research team.

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