The solution structure and dynamics of the DNA-binding domain of HMG-D from Drosophila melanogaster

Jones, David N. M.; Searles, M. Alexandra; Shaw, Graeme L.; Churchill, Mair E. A.; Ner, Sarbjit S.; Keeler, James; Travers, Andrew; Neuhaus, David

doi:10.1016/s0969-2126(00)00063-0

Cited by 115 publications

(147 citation statements)

References 58 publications

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“…The HMG domain is followed by a region that has basic sequences similar to the C-terminal domain of histone H1 and a short C-terminal acidic stretch also seen in HMGB proteins. The NMR structure of the HMG domain from HMG-D is very similar to the previously determined structure of the B domain of HMG1, which revealed the characteristic L-shaped fold formed by three ␣-helices (17)(18)(19)(20)(21).…”

supporting

confidence: 77%

HMG-D and Histone H1 Interplay during Chromatin Assembly and Early Embryogenesis

Ner¹,

Blank²,

Pérez‐Parallé³

et al. 2001

Journal of Biological Chemistry

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HMG-D is an abundant chromosomal protein associated with condensed chromatin during the first nuclear cleavage cycles of the developing Drosophila embryo. We previously suggested that HMG-D might substitute for the linker histone H1 in the preblastoderm embryo and that this substitution might result in the characteristic less compacted chromatin. We have now studied the association of HMG-D with chromatin using a cellfree system for chromatin reconstitution derived from The vertebrate high mobility group proteins of the HMGB class (formerly termed HMG1/2) (1) are relatively abundant nuclear DNA-binding proteins that bend DNA substantially and appear to act primarily as architectural facilitators in the assembly of nucleoprotein complexes (recently reviewed in Refs. 2-4). There is direct evidence that these proteins facilitate the binding of transcription factors to their cognate sites both in vitro and in vivo, but any involvement in the assembly of histone-DNA complexes is less well documented. Circumstantial evidence indicates that certain functions of the vertebrate HMGB proteins (5-7) may parallel those of the linker histone H1 (8). Both have been shown to bind to linker DNA sequences (7, 9, 10), and both stabilize and bind to four-way junctions (11)(12)(13)(14). HMG-D is one of two Drosophila proteins closely related to the vertebrate HMGB proteins but in contrast to these proteins contains only a single HMG DNA-binding domain (6,15,16). The HMG domain is followed by a region that has basic sequences similar to the C-terminal domain of histone H1 and a short C-terminal acidic stretch also seen in HMGB proteins. The NMR structure of the HMG domain from HMG-D is very similar to the previously determined structure of the B domain of HMG1, which revealed the characteristic L-shaped fold formed by three ␣-helices (17-21).High mobility group proteins of the HMGB family bind DNA with little sequence specificity but recognize structural features in DNA (22-24), including cruciforms, kinks, DNA bulges, and bends (22,23,(25)(26)(27)(28). DNA footprint analysis and mutagenesis experiments suggest that HMG domain proteins bind in the minor groove (29). In addition, both crystallization and NMR studies show that HMG-D bending is achieved by the intercalation of hydrophobic residues at two different base steps (21, 30).The addition of histone H1 protein to an extended array of nucleosome core particles promotes its folding into a fiber with an approximate width of 30 nm (31-33). During early Drosophila development, histone H1 is not detectable (34 -36) until nuclear cycles 7/8 (37). Therefore, H1 is not involved in chromatin condensation in these earliest phases of Drosophila development characterized by rapid condensation-decondensation cycles. We have previously suggested that HMG-D could function as a linker protein in the absence of histone H1 in Drosophila (37). In support of this hypothesis, Wolffe and colleagues (10, 38) have postulated a similar role for the Xenopus HMG B1 protein. Thus, as the maternal pool of H...

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supporting

confidence: 77%

HMG-D and Histone H1 Interplay during Chromatin Assembly and Early Embryogenesis

Ner¹,

Blank²,

Pérez‐Parallé³

et al. 2001

Journal of Biological Chemistry

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“…The non-sequence specific HMG boxes of HMG-1 (15,16), S. cerevisiae NHP6A (17) and Drosophila-HMG (18) were found to adopt highly similar structures consisting of three α-helices, arranged in an unusual L-shape or arrow head. Based on the presence of very similar secondary structural elements, an analogous structure was suggested for the sequence-specific HMG box of Sox-5 (12).…”

Section: Introductionmentioning

confidence: 99%

Sequence-specific HMG box factors recognize 10-12 base pair minor groove motifs

Beest

Dooijes

Wetering

et al. 2000

Journal of Biological Chemistry

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SummarySequence specific HMG box factors bind and bend DNA via interactions in the minor groove.3D NMR analyses have provided the structural basis for this interaction. The cognate HMG domain DNA motif is generally believed to span 6 to 8 bases. However, alignment of promotor elements controlled by the yeast genes Ste11 and Rox1 has indicated strict conservation of a larger DNA motif. By site selection, we identify a highly specific 12 bp motif for Ste11:AGAACAAAGAAA. Similarly, we show that Tcf1, MatMc and Sox4 bind unique, highly specific DNA motifs of 12, 12 and 10 bp respectively. Footprinting with a deletion mutant of Ste11 reveals a novel interaction between the 3' base pairs of the extended DNA motif and amino acids Cterminal to the HMG domain. The sequence-specific interaction of Ste11 with these 3' base pairs contributes significantly to binding and bending of the DNA motif.

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“…The ®rst 74 residues of HMG-D, which comprise the HMG-box domain, were expressed and puri®ed as described previously (Dow et al, 1997;Jones et al, 1994). To increase yields of the unoxidized protein, chemical reduction of the methionine oxide was performed by incubating the protein at 298 K with 0.725 M n-methyl mercaptoacetamide buffered at pH 7.0 for 72 h (Houghten & Li, 1979).…”

Section: Protein and Dna Puri®cationmentioning

confidence: 99%

“…HMG-D is a chromosomal protein and, like other HMG proteins, it preferentially binds to DNA structures which are pre-bent and underwound (Churchill et al, , 1999Payet & Travers, 1997;Wolfe et al, 1995). HMG-D contains only a single copy of the HMG-box DNA-binding domain (Ner & Travers, 1994;Wagner et al, 1992) at the N-terminus, which is followed by a`tail' region which has`basic motifs' similar to the C-terminal domain of histone H1 and a C-terminal acidic stretch similar to those in HMG1/2. The structures of the HMG-domain of HMG-D and HMG1 have been determined by NMR (Hardman et al, 1995;Jones et al, 1994;Read et al, 1993;Weir et al, 1993), revealing an L-shaped fold comprised of three helices held together by two hydrophobic cores.…”

Section: Introductionmentioning

confidence: 99%

“…HMG-D contains only a single copy of the HMG-box DNA-binding domain (Ner & Travers, 1994;Wagner et al, 1992) at the N-terminus, which is followed by a`tail' region which has`basic motifs' similar to the C-terminal domain of histone H1 and a C-terminal acidic stretch similar to those in HMG1/2. The structures of the HMG-domain of HMG-D and HMG1 have been determined by NMR (Hardman et al, 1995;Jones et al, 1994;Read et al, 1993;Weir et al, 1993), revealing an L-shaped fold comprised of three helices held together by two hydrophobic cores. The structures of complexes of sequence-speci®c HMG-domains, LEF-1 and SRY, bound to DNA have also been determined by NMR and reveal a common protein fold and severe protein-induced DNA bending toward the major groove (Love et al, 1995;Werner, Bianchi et al, 1995;Werner, Huth et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Co-crystallization and preliminary crystallographic analysis of the high mobility group domain of HMG-D bound to DNA

Murphy

Sehy

Dow

et al. 1999

Acta Crystallogr D Biol Cryst

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Structural studies are essential to understand mechanisms of nonsequence-speci®c DNA binding used by chromosomal proteins. A non-histone high-mobility group (HMG) chromosomal protein from Drosophila melanogaster, HMG-D, binds duplex DNA in a nonsequence-speci®c fashion. The DNA-binding domain of HMG-D has been co-crystallized with a duplex DNA fragment in the primitive orthorhombic space group P2 1 2 1 2 1 , with unit-cell dimensions a = 43.74, b = 53.80, c = 86.84 A Ê . Data have been collected to 2.20 A Ê at 99 K, with diffraction observed to at least 2.0 A Ê . Heavy-atom derivative crystals have been obtained by co-crystallization with oligonucleotides halogenated at major-groove positions near the end of the DNA.

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The solution structure and dynamics of the DNA-binding domain of HMG-D from Drosophila melanogaster

Cited by 115 publications

References 58 publications

HMG-D and Histone H1 Interplay during Chromatin Assembly and Early Embryogenesis

HMG-D and Histone H1 Interplay during Chromatin Assembly and Early Embryogenesis

Sequence-specific HMG box factors recognize 10-12 base pair minor groove motifs

Co-crystallization and preliminary crystallographic analysis of the high mobility group domain of HMG-D bound to DNA

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