Title
Conformational stability of neuroglobin helix F possible effects on the folding pathway within the globin family Conformational stability of neuroglobin helix F possible effects on the folding pathway within the globin family
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Berlin ,
Subject
Biology
Human medicine
Source (journal)
The FEBS journal. - Berlin
Volume/pages
276(2009) :18 , p. 5177-5190
ISSN
1742-464X
ISI
000269366500015
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Neuroglobin is a recently discovered member of the globin family, mainly observed in neurons and retina. Despite the low sequence identity (less than 20% over the whole sequence for the human proteins), the general fold of neuroglobin closely resembles that of myoglobin. The latter is a paradigmatic protein for folding studies, whereas much less is known about the neuroglobin folding pathway. In this work, we show how the structural features of helix F in neuroglobin and myoglobin could represent a pivotal difference in their folding pathways. Former studies widely documented that myoglobin lacks helix F in the apo form. In this study, limited proteolysis experiments on aponeuroglobin showed that helix F does not undergo proteolytic cleavage, suggesting that, also in the apo form, this helix maintains a rigid and structured conformation. To understand better the structural properties of helices F in the two proteins, we analyzed peptides encompassing helix F of neuroglobin and myoglobin in the wild-type and mutant forms. NMR and CD experiments revealed a helical conformation for neuroglobin helix F peptide, at both pH 7 and pH 2, absent in the myoglobin peptide. In particular, NMR data suggest a secondary structure stabilization effect caused by hydrophobic interactions involving Tyr88, Leu89 and Leu92. Molecular dynamics simulations performed on the apo and holo forms of the two proteins reveal the persistence of helix F in neuroglobin even in the absence of heme. Conversely myoglobin shows a higher mobility of the N-terminus of helix F on heme removal, which leads to the loss of secondary structure.
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000269366500015&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000269366500015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000269366500015&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle