Linked Life Data

9680483

Source:http://linkedlifedata.com/resource/pubmed/id/9680483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-8-20
pubmed:abstractText
The oncoprotein c-Myc (a member of the helix-loop-helix-leucine zipper (b-HLH-LZ) family of transcription factors) must heterodimerize with the b-HLH-LZ Max protein to bind DNA and activate transcription. It has been shown that the LZ domains of the c-Myc and Max proteins specifically form a heterodimeric LZ at 20 degreesC and neutral pH. This suggests that the LZ domains of the c-Myc and Max proteins are playing an important role in the heterodimerization of the corresponding gene products in vivo. Initially, to gain an insight into the energetics of heterodimerization, we studied the stability of N-terminal disulfide-linked versions of the c-Myc and Max homodimeric LZs and c-Myc-Max heterodimeric LZ by fitting the temperature-induced denaturation curves monitored by circular dichroism spectroscopy. The c-Myc LZ does not homodimerize (as previously reported) and the c-Myc-Max heterodimeric LZ is more stable than the Max homodimeric LZ at 20 degreesC and pH 7.0. In order to determine the critical interhelical interactions responsible for the molecular recognition between the c-Myc and Max LZs, the solution structure of the disulfide-linked c-Myc-Max heterodimeric LZ was solved by two-dimensional 1H-NMR techniques at 25 degreesC and pH 4.7. Both LZs are alpha-helical and the tertiary structure depicts the typical left-handed super-helical twist of a two-stranded parallel alpha-helical coiled-coil. A buried salt bridge involving a histidine on the Max LZ and two glutamate residues on the c-Myc LZ is observed at the interface of the heterodimeric LZ. A buried H-bond between an asparagine side-chain and a backbone carbonyl is also observed. Moreover, evidence for e-g interhelical salt bridges is reported. These specific interactions give insights into the preferential heterodimerization process of the two LZs. The low stabilities of the Max homodimeric LZ and the c-Myc-Max heterodimeric LZ as well as the specific interactions observed are discussed with regard to regulation of transcription in this family of transcription factors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press.
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9680483-Amino Acid Sequence, pubmed-meshheading:9680483-Basic-Leucine Zipper Transcription Factors, pubmed-meshheading:9680483-Binding Sites, pubmed-meshheading:9680483-DNA-Binding Proteins, pubmed-meshheading:9680483-Dimerization, pubmed-meshheading:9680483-Helix-Loop-Helix Motifs, pubmed-meshheading:9680483-Leucine Zippers, pubmed-meshheading:9680483-Macromolecular Substances, pubmed-meshheading:9680483-Magnetic Resonance Spectroscopy, pubmed-meshheading:9680483-Models, Molecular, pubmed-meshheading:9680483-Molecular Sequence Data, pubmed-meshheading:9680483-Protein Conformation, pubmed-meshheading:9680483-Protein Structure, Secondary, pubmed-meshheading:9680483-Protein Structure, Tertiary, pubmed-meshheading:9680483-Proto-Oncogene Proteins c-myc, pubmed-meshheading:9680483-Solutions, pubmed-meshheading:9680483-Thermodynamics, pubmed-meshheading:9680483-Transcription Factors
pubmed:year
1998
pubmed:articleTitle
Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper.
pubmed:affiliation
The Protein Engineering Network of Centres of Excellence, Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't