1zy2: Difference between revisions

Revision as of 17:20, 21 February 2008

Crystal structure of the phosphorylated receiver domain of the transcription regulator NtrC1 from Aquifex aeolicus

OverviewOverview

Only a few transcriptional regulatory proteins have been characterized in extremely hyperthermophilic organisms, and most function as repressors. Structural features of the NtrC1 protein from the hyperthermophilic bacterium Aquifex aeolicus suggested that this protein functions similarly to the sigma(54)-polymerase activator DctD of Sinorhizobium meliloti. Here, we demonstrate that NtrC1 is an enzyme that hydrolyzes ATP to activate initiation of transcription by sigma(54)-holoenzyme. New structural data, including small-angle solution scattering data and the crystal structure of the phosphorylated receiver domain, show that NtrC1 uses a signal transduction mechanism very similar to that of DctD to control assembly of its AAA+ ATPase domain. As for DctD, the off-state of NtrC1 depends upon a tight dimer of the receiver domain to repress oligomerization of an intrinsically competent ATPase domain. Activation of NtrC1 stabilizes an alternative dimer configuration of the receiver domain that is very similar to the on-state dimers of the DctD and FixJ receiver domains. This alternative dimer appears to relieve repression of the ATPase domain by disrupting the off-state dimerization interface along the helical linker region between receiver and ATPase domains. Bacterial enhancer binding proteins typically have two linker sequences, one between N-terminal regulatory and central ATPase domains, and one between the central ATPase and C-terminal DNA binding domains. Sequence analyses reveal an intriguing correlation between the negative regulation mechanism of NtrC1 and DctD, and a structured N-terminal linker and unstructured C-terminal one; conversely, the very different, positive mechanism present in NtrC protein occurs in the context of an unstructured N-terminal linker and a structured C-terminal one. In both cases, the structured linkers significantly contribute to the stability of the off-state dimer conformation. These analyses also raise the possibility that a structured linker between N-terminal regulatory and central output domains is used frequently in regulatory proteins from hyperthermophilic organisms.

About this StructureAbout this Structure

1ZY2 is a Single protein structure of sequence from Aquifex aeolicus with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Negative regulation of AAA + ATPase assembly by two component receiver domains: a transcription activation mechanism that is conserved in mesophilic and extremely hyperthermophilic bacteria., Doucleff M, Chen B, Maris AE, Wemmer DE, Kondrashkina E, Nixon BT, J Mol Biol. 2005 Oct 21;353(2):242-55. PMID:16169010

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 ==Overview==
-Only a few transcriptional regulatory proteins have been characterized in, extremely hyperthermophilic organisms, and most function as repressors., Structural features of the NtrC1 protein from the hyperthermophilic, bacterium Aquifex aeolicus suggested that this protein functions similarly, to the sigma(54)-polymerase activator DctD of Sinorhizobium meliloti., Here, we demonstrate that NtrC1 is an enzyme that hydrolyzes ATP to, activate initiation of transcription by sigma(54)-holoenzyme. New, structural data, including small-angle solution scattering data and the, crystal structure of the phosphorylated receiver domain, show that NtrC1, uses a signal transduction mechanism very similar to that of DctD to, control assembly of its AAA+ ATPase domain. As for DctD, the off-state of, NtrC1 depends upon a tight dimer of the receiver domain to repress, oligomerization of an intrinsically competent ATPase domain. Activation of, NtrC1 stabilizes an alternative dimer configuration of the receiver domain, that is very similar to the on-state dimers of the DctD and FixJ receiver, domains. This alternative dimer appears to relieve repression of the, ATPase domain by disrupting the off-state dimerization interface along the, helical linker region between receiver and ATPase domains. Bacterial, enhancer binding proteins typically have two linker sequences, one between, N-terminal regulatory and central ATPase domains, and one between the, central ATPase and C-terminal DNA binding domains. Sequence analyses, reveal an intriguing correlation between the negative regulation mechanism, of NtrC1 and DctD, and a structured N-terminal linker and unstructured, C-terminal one; conversely, the very different, positive mechanism present, in NtrC protein occurs in the context of an unstructured N-terminal linker, and a structured C-terminal one. In both cases, the structured linkers, significantly contribute to the stability of the off-state dimer, conformation. These analyses also raise the possibility that a structured, linker between N-terminal regulatory and central output domains is used, frequently in regulatory proteins from hyperthermophilic organisms.
+Only a few transcriptional regulatory proteins have been characterized in extremely hyperthermophilic organisms, and most function as repressors. Structural features of the NtrC1 protein from the hyperthermophilic bacterium Aquifex aeolicus suggested that this protein functions similarly to the sigma(54)-polymerase activator DctD of Sinorhizobium meliloti. Here, we demonstrate that NtrC1 is an enzyme that hydrolyzes ATP to activate initiation of transcription by sigma(54)-holoenzyme. New structural data, including small-angle solution scattering data and the crystal structure of the phosphorylated receiver domain, show that NtrC1 uses a signal transduction mechanism very similar to that of DctD to control assembly of its AAA+ ATPase domain. As for DctD, the off-state of NtrC1 depends upon a tight dimer of the receiver domain to repress oligomerization of an intrinsically competent ATPase domain. Activation of NtrC1 stabilizes an alternative dimer configuration of the receiver domain that is very similar to the on-state dimers of the DctD and FixJ receiver domains. This alternative dimer appears to relieve repression of the ATPase domain by disrupting the off-state dimerization interface along the helical linker region between receiver and ATPase domains. Bacterial enhancer binding proteins typically have two linker sequences, one between N-terminal regulatory and central ATPase domains, and one between the central ATPase and C-terminal DNA binding domains. Sequence analyses reveal an intriguing correlation between the negative regulation mechanism of NtrC1 and DctD, and a structured N-terminal linker and unstructured C-terminal one; conversely, the very different, positive mechanism present in NtrC protein occurs in the context of an unstructured N-terminal linker and a structured C-terminal one. In both cases, the structured linkers significantly contribute to the stability of the off-state dimer conformation. These analyses also raise the possibility that a structured linker between N-terminal regulatory and central output domains is used frequently in regulatory proteins from hyperthermophilic organisms.
 ==About this Structure==
@@ Line 16: / Line 16: @@
 [[Category: Doucleff, M.]]
 [[Category: Kondrashkina, E.]]
-[[Category: Maris, A.E.]]
+[[Category: Maris, A E.]]
-[[Category: Nixon, B.T.]]
+[[Category: Nixon, B T.]]
-[[Category: Wemmer, D.E.]]
+[[Category: Wemmer, D E.]]
 [[Category: MG]]
 [[Category: ntrc]]
@@ Line 25: / Line 25: @@
 [[Category: two-component signaling]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 17:45:19 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:20:11 2008''