Content area
Full Text
ABSTRACT Cooperativity plays an important role in the action of proteins bound to DNA. A simple mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations, is proposed. These proteins are not in direct physical contact. DNA segments intercalating bound proteins are modeled as a worm-like chain, which is free to deform in two dimensions. The tension-controlled protein-protein interaction is the consequence of two effects produced by the protein binding. The first is the introduction of a bend in the host DNA and the second is the modification of the bending modulus of the DNA in the immediate vicinity of the bound protein. The interaction between two bound proteins may be either attractive or repulsive, depending on their relative orientation on the DNA. Applied tension controls both the strength and the range of protein-protein interactions in this model. Properties of the cooperative interaction are discussed, along with experimental implications.
INTRODUCTION
The cooperative binding of proteins to DNA plays a significant role in the regulation of gene expression (OwenHughes and Workman, 1994) because it allows a sensitive response to small changes in protein concentration. In particular, it is well known that transcription factor proteins (Lodish et al., 1995) exhibit a significant level of cooperativity (Sun et al., 1997). The structural basis of the cooperativity is not fully understood (Sun et al., 1997), but it is known that long-range cooperativity is possible through loops (Schlief, 1992), formed as the result of association between two DNA-binding proteins. Looping is also believed to play an important role in gene access control. Cooperativity at shorter distances may be related to specific protein-protein interactions or to a generic cooperativity resulting from structural distortions induced by the binding of a protein to DNA (Lilley, 1995; Nelson, 1995). For example, the binding of transcription regulation proteins such as the important TATA-box promoters (TPB) involves amino acid intercalation into the stack of basepairs (Kim et al., 1993; Werner et al., 1996). The result is that kinks are produced in the form of sharp local bending angles in the DNA strand. This deformation may permit a better fit for other DNA-associating proteins, such as the polymerases. Disruptions of the basepair stacking sequence have no effect...