1cmo

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(New page: 200px<br /> <applet load="1cmo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cmo" /> '''IMMUNOGLOBULIN MOTIF DNA-RECOGNITION AND HE...)
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'''IMMUNOGLOBULIN MOTIF DNA-RECOGNITION AND HETERODIMERIZATION FOR THE PEBP2/CBF RUNT-DOMAIN'''<br />
'''IMMUNOGLOBULIN MOTIF DNA-RECOGNITION AND HETERODIMERIZATION FOR THE PEBP2/CBF RUNT-DOMAIN'''<br />
==Overview==
==Overview==
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The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor, (CBF) is a heterodimeric enhancer binding protein that is associated with, genetic regulation of hematopoiesis and osteogenesis. Aberrant forms of, PEBP2/CBF are implicated in the cause of the acute human leukemias and in, a disorder of bone development known as cleidocranial dysplasia. The, common denominator in the natural and mutant forms of this protein is a, highly conserved domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is responsible for both DNA binding and heterodimerization with the, beta subunit of PEBP2/CBF. The three-dimensional structure of the RD bound, to DNA has been determined to be an S-type immunoglobulin fold, establishing a structural relationship between the RD and the core DNA, binding domains of NF-kappaB, NFAT1, p53 and the STAT proteins. NMR, spectroscopy of a 43.6 kD RD-beta-DNA ternary complex identified the, surface of the RD in contact with the beta subunit, suggesting a mechanism, for the enhancement of RD DNA binding by beta. Analysis of leukemogenic, mutants within the RD provides molecular insights into the role of this, factor in leukemogenesis and cleidocranial dysplasia.
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The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor (CBF) is a heterodimeric enhancer binding protein that is associated with genetic regulation of hematopoiesis and osteogenesis. Aberrant forms of PEBP2/CBF are implicated in the cause of the acute human leukemias and in a disorder of bone development known as cleidocranial dysplasia. The common denominator in the natural and mutant forms of this protein is a highly conserved domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is responsible for both DNA binding and heterodimerization with the beta subunit of PEBP2/CBF. The three-dimensional structure of the RD bound to DNA has been determined to be an S-type immunoglobulin fold, establishing a structural relationship between the RD and the core DNA binding domains of NF-kappaB, NFAT1, p53 and the STAT proteins. NMR spectroscopy of a 43.6 kD RD-beta-DNA ternary complex identified the surface of the RD in contact with the beta subunit, suggesting a mechanism for the enhancement of RD DNA binding by beta. Analysis of leukemogenic mutants within the RD provides molecular insights into the role of this factor in leukemogenesis and cleidocranial dysplasia.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1CMO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CMO OCA].
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1CMO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CMO OCA].
==Reference==
==Reference==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Chait, B.T.]]
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[[Category: Chait, B T.]]
[[Category: Gupta, V.]]
[[Category: Gupta, V.]]
[[Category: Ito, Y.]]
[[Category: Ito, Y.]]
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[[Category: Kim, W.Y.]]
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[[Category: Kim, W Y.]]
[[Category: Nagata, T.]]
[[Category: Nagata, T.]]
[[Category: Sali, A.]]
[[Category: Sali, A.]]
[[Category: Shigesada, K.]]
[[Category: Shigesada, K.]]
[[Category: Sorce, D.]]
[[Category: Sorce, D.]]
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[[Category: Werner, M.H.]]
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[[Category: Werner, M H.]]
[[Category: hematopoiesis]]
[[Category: hematopoiesis]]
[[Category: ig-fold]]
[[Category: ig-fold]]
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[[Category: transcription factor]]
[[Category: transcription factor]]
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Revision as of 10:07, 21 February 2008


1cmo

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IMMUNOGLOBULIN MOTIF DNA-RECOGNITION AND HETERODIMERIZATION FOR THE PEBP2/CBF RUNT-DOMAIN

Contents

Overview

The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor (CBF) is a heterodimeric enhancer binding protein that is associated with genetic regulation of hematopoiesis and osteogenesis. Aberrant forms of PEBP2/CBF are implicated in the cause of the acute human leukemias and in a disorder of bone development known as cleidocranial dysplasia. The common denominator in the natural and mutant forms of this protein is a highly conserved domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is responsible for both DNA binding and heterodimerization with the beta subunit of PEBP2/CBF. The three-dimensional structure of the RD bound to DNA has been determined to be an S-type immunoglobulin fold, establishing a structural relationship between the RD and the core DNA binding domains of NF-kappaB, NFAT1, p53 and the STAT proteins. NMR spectroscopy of a 43.6 kD RD-beta-DNA ternary complex identified the surface of the RD in contact with the beta subunit, suggesting a mechanism for the enhancement of RD DNA binding by beta. Analysis of leukemogenic mutants within the RD provides molecular insights into the role of this factor in leukemogenesis and cleidocranial dysplasia.

Disease

Known diseases associated with this structure: Leukemia, acute myeloid OMIM:[151385], Platelet disorder, familial, with associated myeloid malignancy OMIM:[151385], Rheumatoid arthritis, susceptibility to OMIM:[151385]

About this Structure

1CMO is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Immunoglobulin motif DNA recognition and heterodimerization of the PEBP2/CBF Runt domain., Nagata T, Gupta V, Sorce D, Kim WY, Sali A, Chait BT, Shigesada K, Ito Y, Werner MH, Nat Struct Biol. 1999 Jul;6(7):615-9. PMID:10404214

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