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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-2-22
pubmed:abstractText
The amino-terminal region of microsomal P450s contains three distinct sequence motifs, the signal-anchor sequence (SA), the basic sequence (BS), and the proline-rich sequence (PR). Studies with two P450s of the CYP2C subfamily, P4502C11 (CYP2C11) and P4502C2 (CYP2C2), have indicated that upon expression in eukaryotic cells (yeast, COS cells, and insect cells), specific proline residues in PR are important for proper folding. In the present study, we have established that the PR region in a very different CYP gene family, P450c17 (CYP17), is also important for efficient folding. These studies have been carried out using expression in Escherichia coli. Using P4502C11, we have established that the folding requirements for P450s in bacteria are very similar to those in eukaryotic cells. Interestingly, when the PR from P450c17 is swapped for that of P4502C11 and visa versa, complete misfolding is observed. However, both the BS and SA can be swapped between these P450s without affecting folding. After proper folding of P450c17, removal of the PR by factor Xa protease has no effect on the maintenance of the P450 structure. Inspection of the sequences of many different CYP gene families indicates that the PR sequence is conserved within a gene family but varies considerably between families. We conclude that PR is important for directing the folding pathway leading to the functional P450, but not for maintaining the functional form.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-924X
pubmed:author
pubmed:issnType
Print
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
259-69
pubmed:dateRevised
2007-12-19
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Microsomal p450s use specific proline-rich sequences for efficient folding, but not for maintenance of the folded structure.
pubmed:affiliation
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. k-kusano@hhc.eisai.co.jp
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't