Abstract:
:In the DNA recognition mode of C(2)H(2)-type zinc fingers, the finger-finger connection region, consisting of the histidine spacing (HX(3-5)H) and linker, would be important for determining the orientation of the zinc finger domains. To clarify the influence of spacing between two ligand histidines in the DNA binding, we exchanged the histidine spacing between Sp1 and GLI zinc fingers, which have an HX(3)H-TGEKK linker (typical) and an HX(4)H-SNEKP linker (atypical), respectively. A significant decrease in the DNA binding affinity and specificity is found in Sp1-type peptides, whereas GLI-type peptides show a mild reduction. To evaluate the effect of the linker characteristics, we further designed Sp1-type mutants with an SNEKP linker. As a result, the significant effect of the histidine spacing in Sp1-type peptides was reduced. These results demonstrate that (1) the histidine spacing significantly affects the DNA binding of zinc finger proteins and (2) the histidine spacing and the following linker regions are one effective target for regulating the DNA recognition mode of zinc finger proteins.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Shiraishi Y,Imanishi M,Sugiura Ydoi
10.1021/bi035999ssubject
Has Abstractpub_date
2004-05-25 00:00:00pages
6352-9issue
20eissn
0006-2960issn
1520-4995journal_volume
43pub_type
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