1au7: Difference between revisions

Revision as of 12:48, 21 February 2008

PIT-1 MUTANT/DNA COMPLEX

OverviewOverview

Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix alpha1 and in the loop between helices alpha3 and alpha4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.

About this StructureAbout this Structure

1AU7 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility., Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK, Genes Dev. 1997 Jan 15;11(2):198-212. PMID:9009203

Page seeded by OCA on Thu Feb 21 11:48:20 2008

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OCA

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-[[Image:1au7.gif|left|200px]]<br /><applet load="1au7" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1au7.gif|left|200px]]<br /><applet load="1au7" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1au7, resolution 2.300&Aring;" />
 '''PIT-1 MUTANT/DNA COMPLEX'''<br />
 ==Overview==
-Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical, developmental functions based on binding to diverse DNA elements in its, target genes. Here we report a high resolution X-ray analysis of the Pit-1, POU domain bound to a DNA element as a homodimer. This analysis reveals, that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than, opposite faces of the DNA as in Oct-1. This is accomplished by different, spacing and orientation of the POU-specific domain. Contrary to previous, predictions, the dimerization interface involves the carboxyl terminus of, the DNA recognition helix of the homeodomain, which in an extended, conformation interacts with specific residues at the amino terminus of, helix alpha1 and in the loop between helices alpha3 and alpha4 of the, POU-specific domain of the symmetry related monomer. These features, suggest the molecular basis of disease-causing mutations in Pit-1 and, provide potential basis for the flexible allostery between protein domains, and DNA sites in the activation of target genes.
+Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix alpha1 and in the loop between helices alpha3 and alpha4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.
 ==About this Structure==
-AU7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AU7 OCA].
+AU7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AU7 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Rattus norvegicus]]
 [[Category: Single protein]]
-[[Category: Aggarwal, A.K.]]
+[[Category: Aggarwal, A K.]]
-[[Category: Jacobson, E.M.]]
+[[Category: Jacobson, E M.]]
 [[Category: Leon-Del-Rio, A.]]
 [[Category: Li, P.]]
-[[Category: Rosenfeld, M.G.]]
+[[Category: Rosenfeld, M G.]]
 [[Category: complex (dna-binding protein/dna)]]
 [[Category: cphd]]
@@ Line 24: / Line 24: @@
 [[Category: transcription factor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 11:08:09 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:48:20 2008''