TY - JOUR
T1 - Crystal Structure of the Mor Protein of Bacteriophage Mu, a Member of the Mor/C Family of Transcription Activators
AU - Kumaraswami, Muthiah
AU - Howe, Martha M.
AU - Park, Hee Won
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/4/16
Y1 - 2004/4/16
N2 - Transcription from the middle promoter, Pm, of bacteriophage Mu requires the phage-encoded activator protein Mor and bacterial RNA polymerase. Mor is a sequence-specific DNA-binding protein that mediates transcription activation through its interactions with the C-terminal domains of the α and σ subunits of bacterial RNA polymerase. Here we present the first structure for a member of the Mor/C family of transcription activators, the crystal structure of Mor to 2.2-Å resolution. Each monomer of the Mor dimer is composed of two domains, the N-terminal dimerization domain and C-terminal DNA-binding domain, which are connected by a linker containing a β strand. The N-terminal dimerization domain has an unusual mode of dimerization; helices α1 and α2 of both monomers are intertwined to form a four-helix bundle, generating a hydrophobic core that is further stabilized by antiparallel interactions between the two β strands. Mutational analysis of key leucine residues in helix α1 demonstrated a role for this hydrophobic core in protein solubility and function. The C-terminal domain has a classical helix-turn-helix DNA-binding motif that is located at opposite ends of the elongated dimer. Since the distance between the two helix-turn-helix motifs is too great to allow binding to two adjacent major grooves of the 16-bp Mor-binding site, we propose that conformational changes in the protein and DNA will be required for Mor to interact with the DNA. The highly conserved glycines flanking the β strand may act as pivot points, facilitating the conformational changes of Mor, and the DNA may be bent.
AB - Transcription from the middle promoter, Pm, of bacteriophage Mu requires the phage-encoded activator protein Mor and bacterial RNA polymerase. Mor is a sequence-specific DNA-binding protein that mediates transcription activation through its interactions with the C-terminal domains of the α and σ subunits of bacterial RNA polymerase. Here we present the first structure for a member of the Mor/C family of transcription activators, the crystal structure of Mor to 2.2-Å resolution. Each monomer of the Mor dimer is composed of two domains, the N-terminal dimerization domain and C-terminal DNA-binding domain, which are connected by a linker containing a β strand. The N-terminal dimerization domain has an unusual mode of dimerization; helices α1 and α2 of both monomers are intertwined to form a four-helix bundle, generating a hydrophobic core that is further stabilized by antiparallel interactions between the two β strands. Mutational analysis of key leucine residues in helix α1 demonstrated a role for this hydrophobic core in protein solubility and function. The C-terminal domain has a classical helix-turn-helix DNA-binding motif that is located at opposite ends of the elongated dimer. Since the distance between the two helix-turn-helix motifs is too great to allow binding to two adjacent major grooves of the 16-bp Mor-binding site, we propose that conformational changes in the protein and DNA will be required for Mor to interact with the DNA. The highly conserved glycines flanking the β strand may act as pivot points, facilitating the conformational changes of Mor, and the DNA may be bent.
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U2 - 10.1074/jbc.M313555200
DO - 10.1074/jbc.M313555200
M3 - Article
C2 - 14729670
AN - SCOPUS:1942533431
SN - 0021-9258
VL - 279
SP - 16581
EP - 16590
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 16
ER -