linker peptide in two-domain fusion protein

Simon Brocklehurst smb18 at mbfs.bio.cam.ac.uk
Mon Jul 26 05:32:36 EST 1993


girish at imtech.ernet.in (GIRISH SAHNI, SCIENTIST, IMTECH SECTOR 39-A, CHANDIGARH 160014, INDIA) writes:

>Dear Freind, Hi there:

>I need some suggestions for designing a linker sequence between two
>independently folded protein domains in a fusion (gene) construct.
>Perhaps we would have to try a few candidate sequences (3-10 AA long)
>with varying degrees of flexibility/rigidity, since we cannot predict
>a priori what the effect may be on unwanted aggregation or steric 
>hindrance associated with the final hybrid protein. Sources where I
>might ponder these aspects will be welcome, as would actual AA sequences
>of possible linker peptides.    Thank you
>                                           Girish Sahni IMTECH, India
>                                             Email: "girish at imtech.ernet.in"

There are probably two kinds of sequence that you might want to explore.

1) Sequences made up of Ala and Pro.  By varying the number of Ala-Pro
   pairs you can modulate the flexibility of the linker.

2)  Sequences made up of charged amino acid residues e.g. mixing
    Glu and Lys.  It is more difficult to rationilise how flexibility
    can be modulated by sequence variation in this case.

    Both these types of sequence are common in long (30-40 aa) linkers
    joining independently folded domains in multifunctional polypeptides.

     A good reference to start with is the review by Richard Perham
     "Domains, motifs and linkers in 2-oxo acid dehydrogenase multienzyme
      complexes: a paradigm in the design of a multifunctional protein"
      Biochemistry 30, 8501-8512


Simon M. Brocklehurst
Cambridge Centre for Molecular Recognition
Dept. of Biochemistry
University of Cambridge
Tennis Court Road
Cambridge
UK



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