Review
HMG1 and 2, and related ‘architectural’ DNA-binding proteins

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Abstract

The HMG-box proteins, one of the three classes of high mobility group (HMG) chromosomal proteins1, bend DNA and bind preferentially to distorted DNA structures. The proteins appear to act primarily as architectural facilitators in the assembly of nucleoprotein complexes; for example, in effecting recombination and in the initiation of transcription. HMG-box proteins might be targeted to particular DNA sites in chromatin by either protein–protein interactions or recognition of specific DNA structures.

Section snippets

The HMG-box domain

The global fold of the HMG box is well conserved and consists of three α-helices arranged in an L-shape (Fig. 2) 6. The structure of the B domain of HMG1 is highly similar to the HMG-box domains of S. cerevisiae Nhp6ap and Drosophila HMG-D and, to a lesser extent, to the sequence-specific (e.g. SRY and LEF-1) HMG-boxes. However, the A domain of HMG1, despite having a broadly similar fold, differs significantly from the B domain in the relative disposition of helices I and II and in the

Structural basis for DNA binding and bending

How do the B-type HMG-box domains bend DNA by over 90° within a single turn of the DNA duplex? In B-type domain complexes, as exemplified by the sequence-specific HMG boxes (e.g. LEF-1), the DNA-binding face of the domain presents a hydrophobic surface that conforms to a wide, shallow minor groove. In the centre of this surface, a hydrophobic wedge, usually consisting of four spatially close residues, is inserted deep into the minor groove. One of the residues located towards the N-terminal end

Functional roles of HMG1 and HMG2

To what extent do the characteristic DNA-binding properties of the HMG-box domain reflect the biological roles of the abundant HMG-domain proteins? One proposed general function of these proteins is to overcome the barrier imposed by the axial rigidity of DNA and thereby promote the formation of complex nucleoprotein assemblies containing tightly bent DNA (32). Such a role probably requires that the bend be precisely placed, a displacement of the binding site by even 1 bp would alter the

HMG-box proteins and chromatin

HMG1 was first described as a ‘non-histone chromosomal protein’ and has been implicated in the maintenance and establishment of chromatin structure 1 (in addition to the more recently identified roles summarized in Table 2). In S. cerevisiae, the loss of the related two-box protein Hmo1p results in a general increase in the sensitivity of chromatin to digestion by micrococcal nuclease 3, suggesting that Hmo1p might act as a structural component. The role of the HMG proteins might be to bend DNA

Concluding remarks

Work over the past few years has illuminated the molecular basis for the apparently diverse roles of the HMG1 and 2 class of proteins. A major role of these non-sequence specific DNA-binding proteins is to facilitate the formation of complex nucleoprotein assemblies. Such a role has already been described for the sequence-specific HMG-box protein LEF-1, which is involved in the assembly of a multiprotein complex at the T-cell receptor locus TCRα (38). A fundamental difference between the

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