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PDBsum entry 5mpi
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Transcription
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PDB id
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5mpi
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PDB id:
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| Name: |
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Transcription
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Title:
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Structural basis of gene regulation by the grainyhead transcription factor superfamily
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Structure:
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Grainyhead-like protein 1 homolog. Chain: a. Synonym: mammalian grainyhead,nh32,transcription factor cp2-like 2, transcription factor lbp-32. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: grhl1, lbp32, mgr, tfcp2l2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.35Å
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R-factor:
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0.224
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R-free:
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0.252
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Authors:
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Q.Ming,Y.Roske,A.Schuetz,K.Walentin,I.Ibraimi,K.M.Schmidt-Ott, U.Heinemann
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Key ref:
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Q.Ming
et al.
(2018).
Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family.
Nucleic Acids Res,
46,
2082-2095.
PubMed id:
DOI:
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Date:
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16-Dec-16
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Release date:
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17-Jan-18
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PROCHECK
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Headers
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References
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Q9NZI5
(GRHL1_HUMAN) -
Grainyhead-like protein 1 homolog from Homo sapiens
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Seq:
Struc:
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618 a.a.
205 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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DOI no:
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Nucleic Acids Res
46:2082-2095
(2018)
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PubMed id:
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Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family.
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Q.Ming,
Y.Roske,
A.Schuetz,
K.Walentin,
I.Ibraimi,
K.M.Schmidt-Ott,
U.Heinemann.
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ABSTRACT
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Grainyhead (Grh)/CP2 transcription factors are highly conserved in multicellular
organisms as key regulators of epithelial differentiation, organ development and
skin barrier formation. In addition, they have been implicated as being tumor
suppressors in a variety of human cancers. Despite their physiological
importance, little is known about their structure and DNA binding mode. Here, we
report the first structural study of mammalian Grh/CP2 factors. Crystal
structures of the DNA-binding domains of grainyhead-like (Grhl) 1 and Grhl2
reveal a closely similar conformation with immunoglobulin-like core. Both share
a common fold with the tumor suppressor p53, but differ in important structural
features. The Grhl1 DNA-binding domain binds duplex DNA containing the consensus
recognition element in a dimeric arrangement, supporting parsimonious
target-sequence selection through two conserved arginine residues. We elucidate
the molecular basis of a cancer-related mutation in Grhl1 involving one of these
arginines, which completely abrogates DNA binding in biochemical assays and
transcriptional activation of a reporter gene in a human cell line. Thus, our
studies establish the structural basis of DNA target-site recognition by Grh
transcription factors and reveal how tumor-associated mutations inactivate Grhl
proteins. They may serve as points of departure for the structure-based
development of Grh/CP2 inhibitors for therapeutic applications.
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Links
