Linked Life Data

20599545

Source:http://linkedlifedata.com/resource/pubmed/id/20599545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-8-3
pubmed:abstractText
A superfamily of integral membrane proteins is characterized by a conserved tryptophan-rich region (called the WWD domain) in an external loop at the inner membrane surface. The three major members of this family (CcmC, CcmF, and CcsBA) are each involved in cytochrome c biosynthesis, yet the function of the WWD domain is unknown. It has been hypothesized that the WWD domain binds heme to present it to an acceptor protein (apoCcmE for CcmC or apocytochrome c for CcmF and CcsBA) such that the heme vinyl group(s) covalently attaches to the acceptors. Alternative proposals suggest that the WWD domain interacts directly with the acceptor protein (e.g., apoCcmE for CcmC). Here, it is shown that CcmC is only trapped with heme when its cognate acceptor protein CcmE is present. It is demonstrated that CcmE only interacts stably with CcmC when heme is present; thus, specific residues in each protein provide sites of interaction with heme to form this very stable complex. For the first time, evidence that the external WWD domain of CcmC interacts directly with heme is presented. Single and multiple substitutions of completely conserved residues in the WWD domain of CcmC alter the spectral properties of heme in the stable CcmC:heme:CcmE complexes. Moreover, some mutations reduce the binding of heme up to 100%. It is likely that endogenously synthesized heme enters the external WWD domain of CcmC either via a channel within this six-transmembrane-spanning protein or from the membrane. The data suggest that a specific heme channel (i.e., heme binding site within membrane spanning helices) is not present in CcmC, in contrast to the CcsBA protein. We discuss the likelihood that it is not important to protect the heme via trafficking in CcmC whereas it is critical in CcsBA.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
401
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
350-62
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The CcmC:heme:CcmE complex in heme trafficking and cytochrome c biosynthesis.
pubmed:affiliation
Department of Biology, Washington University, Campus Box 1137, 1 Brookings Drive, St Louis, MO 63130, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural