The DNA recognition subunit of a DNA methyltransferase is predominantly a molten globule in the absence of DNA.
Enzyme-catalysed DNA methylation provides an opportunity for the modulation of protein-DNA recognition in biological systems. Recently we have demonstrated that the smaller of the two subunits of the heterodimeric, cytosine-specific DNA methyltransferase, M. AquI, is largely responsible for sequence-specific DNA recognition. Here we present evidence from a series of NMR, fluorescence and circular dichroism spectroscopy experiments that the DNA binding subunit of M. AquI has the characteristics of a molten globule in the absence of the catalytic machinery. In this metastable state this subunit retains its ability to bind DNA in a sequence-specific manner. We believe this finding offers an insight into the structural flexibility which underpins the mechanism of action of these enzymes, and may provide a possible biological role for molten globules in protein function.
Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
D P
DP
Hornby
A
A
Whitmarsh
H
H
Pinarbasi
S M
SM
Kelly
N C
NC
Price
P
P
Shore
G S
GS
Baldwin
J
J
Waltho
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D003600:Cytosol; D005121:Extremities / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008675:Metamorphosis, Biological; D008969:Molecular Sequence Data; D009024:Morphogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013623:Tail / Q000254:growth & development / Q000378:metabolism; D013963:Thyroid Hormones; D014982:Xenopus laevis; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins