The High-Mobility-Group (HMG) chromosomal proteins, which are
common to all eukaryotes, bind DNA in a non-sequence-specific fashion
to promote chromatin function and gene regulation. They interact
directly with nucleosomes and are believed to be modulators of
chromatin structure. They are also important in V(D)J recombination
and in activating a number of regulators of gene expression,
including p. 53, Hox transcription factors and steroid hormone
receptors, by increasing their affinity for DNA. The X-ray crystal
structure, at $2.2^{ resolution, of the HMG-domain of the Drosophila
melanogaster protein, HMG-D, bound to DNA provides the first detailed
view of a chromosomal HMG-domain interacting with linear DNA and
reveals the molecular basis of non-sequence-specific DNA recognition.
Sequence-neutral mechanisms of DNA-binding substitute for
base-specific hydrogen bonds made by equivalent residues of the
sequence-specific HMG-domain protein, Lymphoid Enhancer Factor-1.
The use of multiple intercalations and water mediated DNA contacts
may prove to be generally important mechanisms by which chromosomal
proteins bind to DNA in the minor groove. The relationship between
structure and function as well as specificity in molecular
recognition will also be discussed.