Allosteric Response of DNA Recognition Helices of Catabolite Activator Protein to cAMP and DNA Binding

2020 ◽  
Vol 60 (12) ◽  
pp. 6366-6376
Author(s):  
Akshay Prabhakant ◽  
Abhinandan Panigrahi ◽  
Marimuthu Krishnan
Keyword(s):  
Dna Binding ◽  
Dna Recognition ◽  
Catabolite Activator Protein ◽  
Activator Protein

scholarly journals Catabolite activator protein: DNA binding and transcription activation

2004 ◽  
Vol 14 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Catherine L Lawson ◽  
David Swigon ◽  
Katsuhiko S Murakami ◽  
Seth A Darst ◽  
Helen M Berman ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcription Activation ◽  
Catabolite Activator Protein ◽  
Activator Protein

scholarly journals Structural basis for cAMP-mediated allosteric control of the catabolite activator protein

2009 ◽  
Vol 106 (17) ◽  
pp. 6927-6932 ◽  
Author(s):  
Nataliya Popovych ◽  
Shiou-Ru Tzeng ◽  
Marco Tonelli ◽  
Richard H. Ebright ◽  
Charalampos G. Kalodimos
Keyword(s):  
Dna Binding ◽  
Structural Changes ◽  
Coiled Coil ◽  
Binding Pocket ◽  
Receptor Protein ◽  
Structural Basis ◽  
Allosteric Transition ◽  
Allosteric Control ◽  
Catabolite Activator Protein ◽  
Activator Protein

The cAMP-mediated allosteric transition in the catabolite activator protein (CAP; also known as the cAMP receptor protein, CRP) is a textbook example of modulation of DNA-binding activity by small-molecule binding. Here we report the structure of CAP in the absence of cAMP, which, together with structures of CAP in the presence of cAMP, defines atomic details of the cAMP-mediated allosteric transition. The structural changes, and their relationship to cAMP binding and DNA binding, are remarkably clear and simple. Binding of cAMP results in a coil-to-helix transition that extends the coiled-coil dimerization interface of CAP by 3 turns of helix and concomitantly causes rotation, by ≈60°, and translation, by ≈7 Å, of the DNA-binding domains (DBDs) of CAP, positioning the recognition helices in the DBDs in the correct orientation to interact with DNA. The allosteric transition is stabilized further by expulsion of an aromatic residue from the cAMP-binding pocket upon cAMP binding. The results define the structural mechanisms that underlie allosteric control of this prototypic transcriptional regulatory factor and provide an illustrative example of how effector-mediated structural changes can control the activity of regulatory proteins.

scholarly journals Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.

1992 ◽  
Vol 12 (8) ◽  
pp. 3315-3324 ◽  
Author(s):  
S A Veals ◽  
C Schindler ◽  
D Leonard ◽  
X Y Fu ◽  
R Aebersold ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Proteins ◽  
Dna Recognition ◽  
Interferon Regulatory Factor ◽  
Dna Binding Proteins ◽  
Alpha Interferon ◽  
Cdna Clones ◽  
Regulatory Factor ◽  
Amino Terminal ◽  
Sequence Similarities

Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor-mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3 alpha and ISGF3 gamma. ISGF3 gamma serves as the DNA recognition subunit, while ISGF3 alpha, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3 gamma DNA-binding activity was identified as a 48-kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3 gamma translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3 gamma purified from HeLa cells. Sequencing of ISGF3 gamma cDNA clones revealed significant similarity to the interferon regulatory factor (IRF) family of DNA binding proteins in the amino-terminal 117 residues of ISGF3 gamma. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3 gamma. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3 gamma and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3 gamma, like the natural protein, interacted with HeLa cell ISGF3 alpha to form the mature ISGF3 DNA-binding complex. We suggest that other IRF family members may participate in signaling pathways by interacting with as yet unidentified regulatory subunits analogous to ISGF3 alpha.

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