Suppressed By

M486I [G7]
D515N,Y
D518G
D530Y
D540N
N541S
E559K
E560K,V
D583V
E586K [F11]
QQ593KH [D13]
L596S,P [D13]

E490V/L529S
E492D/D515N/S549R
E581V/L596P

WHERE: The Wrinkle appears in grid H10-11. It is the yellow protuberance emerging from the yellow alpha helix.

WHAT: This is an odd interruption to find in the middle of an alpha helix. It could provide the helix with an 'elbow joint', could conspire to render the helix susceptible to dissolution, or could be a red herring of no interest whatsoever. Deletion impairs function as measured by poor performance in plaque expansion assay.

FRIENDS & RELATIONS: In genetic tests, it behaves similarly to the "Actin binding" mutants E531Q[G12], P536R[G13] and R562H[G12].

Analysis: Note the large number of suppressors that occur to negatively charged (D and E = aspartic acid and glutamic acid) residues in the region 490-590. Why does making this large region less negatively charged counteract the deletion of the Wrinkle? Note also the D518G change--this is immediately adjacent to the wrinkle deletion. It suggests that the loss of the wrinkle may not be important because of the missing GRQPPG amino acids but is instead due to the loss of flexibility at this region. HOWEVER, note that this mutation is also removing a negative residue. In order to clarify the mechanism of this suppressor, we are creating 'delGrink' which replaces the wrinkle sequence with a single G (glycine, the smallest and most mobile amino acid) while leaving D518 intact.

Image: delWrinkle is a primary mutant in the ActBind Mirror