The influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallin.
Identifieur interne : 000777 ( Main/Exploration ); précédent : 000776; suivant : 000778The influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallin.
Auteurs : Blagojce Jovcevski [Australie] ; J. Andrew Aquilina [Australie] ; Justin L P. Benesch [Royaume-Uni] ; Heath Ecroyd [Australie]Source :
- Cell stress & chaperones [ 1466-1268 ] ; 2018.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : alpha-Crystallin B Chain.
- chemical , genetics : alpha-Crystallin B Chain.
- chemical , metabolism : alpha-Crystallin B Chain.
- Humans, Mutation, Protein Domains, Protein Multimerization, Protein Structure, Secondary.
Abstract
αB-Crystallin (HSPB5) is a small heat-shock protein that is composed of dimers that then assemble into a polydisperse ensemble of oligomers. Oligomerisation is mediated by heterologous interactions between the C-terminal tail of one dimer and the core "α-crystallin" domain of another and stabilised by interactions made by the N-terminal region. Comparatively little is known about the latter contribution, but previous studies have suggested that residues in the region 54-60 form contacts that stabilise the assembly. We have generated mutations in this region (P58A, S59A, S59K, R56S/S59R and an inversion of residues 54-60) to examine their impact on oligomerisation and chaperone activity in vitro. By using native mass spectrometry, we found that all the αB-crystallin mutants were assembly competent, populating similar oligomeric distributions to wild-type, ranging from 16-mers to 30-mers. However, circular dichroism spectroscopy, intrinsic tryptophan and bis-ANS fluorescence studies demonstrated that the secondary structure differs to wild type, the 54-60 inversion mutation having the greatest impact. All the mutants exhibited a dramatic decrease in exposed hydrophobicity. We also found that the mutants in general were equally active as the wild-type protein in inhibiting the amorphous aggregation of insulin and seeded amyloid fibrillation of α-synuclein in vitro, except for the 54-60 inversion mutant, which was significantly less effective at inhibiting insulin aggregation. Our data indicate that alterations in the part of the N-terminal region proximal to the core domain do not drastically affect the oligomerisation of αB-crystallin, reinforcing the robustness of αB-crystallin in functioning as a molecular chaperone.
DOI: 10.1007/s12192-018-0889-y
PubMed: 29520626
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000976
- to stream PubMed, to step Curation: 000976
- to stream PubMed, to step Checkpoint: 000737
- to stream Ncbi, to step Merge: 001D56
- to stream Ncbi, to step Curation: 001D56
- to stream Ncbi, to step Checkpoint: 001D56
- to stream Main, to step Merge: 000780
- to stream Main, to step Curation: 000777
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallin.</title><author><name sortKey="Jovcevski, Blagojce" sort="Jovcevski, Blagojce" uniqKey="Jovcevski B" first="Blagojce" last="Jovcevski">Blagojce Jovcevski</name><affiliation wicri:level="1"><nlm:affiliation>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522</wicri:regionArea><wicri:noRegion>2522</wicri:noRegion></affiliation></author><author><name sortKey="Andrew Aquilina, J" sort="Andrew Aquilina, J" uniqKey="Andrew Aquilina J" first="J" last="Andrew Aquilina">J. Andrew Aquilina</name><affiliation wicri:level="1"><nlm:affiliation>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522</wicri:regionArea><wicri:noRegion>2522</wicri:noRegion></affiliation></author><author><name sortKey="Benesch, Justin L P" sort="Benesch, Justin L P" uniqKey="Benesch J" first="Justin L P" last="Benesch">Justin L P. Benesch</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Ecroyd, Heath" sort="Ecroyd, Heath" uniqKey="Ecroyd H" first="Heath" last="Ecroyd">Heath Ecroyd</name><affiliation wicri:level="1"><nlm:affiliation>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522, Australia. heathe@uow.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522</wicri:regionArea><wicri:noRegion>2522</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:29520626</idno><idno type="pmid">29520626</idno><idno type="doi">10.1007/s12192-018-0889-y</idno><idno type="wicri:Area/PubMed/Corpus">000976</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000976</idno><idno type="wicri:Area/PubMed/Curation">000976</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000976</idno><idno type="wicri:Area/PubMed/Checkpoint">000737</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000737</idno><idno type="wicri:Area/Ncbi/Merge">001D56</idno><idno type="wicri:Area/Ncbi/Curation">001D56</idno><idno type="wicri:Area/Ncbi/Checkpoint">001D56</idno><idno type="wicri:Area/Main/Merge">000780</idno><idno type="wicri:Area/Main/Curation">000777</idno><idno type="wicri:Area/Main/Exploration">000777</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallin.</title><author><name sortKey="Jovcevski, Blagojce" sort="Jovcevski, Blagojce" uniqKey="Jovcevski B" first="Blagojce" last="Jovcevski">Blagojce Jovcevski</name><affiliation wicri:level="1"><nlm:affiliation>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522</wicri:regionArea><wicri:noRegion>2522</wicri:noRegion></affiliation></author><author><name sortKey="Andrew Aquilina, J" sort="Andrew Aquilina, J" uniqKey="Andrew Aquilina J" first="J" last="Andrew Aquilina">J. Andrew Aquilina</name><affiliation wicri:level="1"><nlm:affiliation>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522</wicri:regionArea><wicri:noRegion>2522</wicri:noRegion></affiliation></author><author><name sortKey="Benesch, Justin L P" sort="Benesch, Justin L P" uniqKey="Benesch J" first="Justin L P" last="Benesch">Justin L P. Benesch</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OX1 3QZ</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Ecroyd, Heath" sort="Ecroyd, Heath" uniqKey="Ecroyd H" first="Heath" last="Ecroyd">Heath Ecroyd</name><affiliation wicri:level="1"><nlm:affiliation>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522, Australia. heathe@uow.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Northfields Ave, Wollongong, NSW, 2522</wicri:regionArea><wicri:noRegion>2522</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell stress & chaperones</title><idno type="eISSN">1466-1268</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Humans</term><term>Mutation</term><term>Protein Domains</term><term>Protein Multimerization</term><term>Protein Structure, Secondary</term><term>alpha-Crystallin B Chain (chemistry)</term><term>alpha-Crystallin B Chain (genetics)</term><term>alpha-Crystallin B Chain (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Chaîne B de la cristalline alpha ()</term><term>Chaîne B de la cristalline alpha (génétique)</term><term>Chaîne B de la cristalline alpha (métabolisme)</term><term>Domaines protéiques</term><term>Humains</term><term>Multimérisation de protéines</term><term>Mutation</term><term>Structure secondaire des protéines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>alpha-Crystallin B Chain</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Crystallin B Chain</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>alpha-Crystallin B Chain</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Chaîne B de la cristalline alpha</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Chaîne B de la cristalline alpha</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Mutation</term><term>Protein Domains</term><term>Protein Multimerization</term><term>Protein Structure, Secondary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Chaîne B de la cristalline alpha</term><term>Domaines protéiques</term><term>Humains</term><term>Multimérisation de protéines</term><term>Mutation</term><term>Structure secondaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">αB-Crystallin (HSPB5) is a small heat-shock protein that is composed of dimers that then assemble into a polydisperse ensemble of oligomers. Oligomerisation is mediated by heterologous interactions between the C-terminal tail of one dimer and the core "α-crystallin" domain of another and stabilised by interactions made by the N-terminal region. Comparatively little is known about the latter contribution, but previous studies have suggested that residues in the region 54-60 form contacts that stabilise the assembly. We have generated mutations in this region (P58A, S59A, S59K, R56S/S59R and an inversion of residues 54-60) to examine their impact on oligomerisation and chaperone activity in vitro. By using native mass spectrometry, we found that all the αB-crystallin mutants were assembly competent, populating similar oligomeric distributions to wild-type, ranging from 16-mers to 30-mers. However, circular dichroism spectroscopy, intrinsic tryptophan and bis-ANS fluorescence studies demonstrated that the secondary structure differs to wild type, the 54-60 inversion mutation having the greatest impact. All the mutants exhibited a dramatic decrease in exposed hydrophobicity. We also found that the mutants in general were equally active as the wild-type protein in inhibiting the amorphous aggregation of insulin and seeded amyloid fibrillation of α-synuclein in vitro, except for the 54-60 inversion mutant, which was significantly less effective at inhibiting insulin aggregation. Our data indicate that alterations in the part of the N-terminal region proximal to the core domain do not drastically affect the oligomerisation of αB-crystallin, reinforcing the robustness of αB-crystallin in functioning as a molecular chaperone.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Oxfordshire</li></region><settlement><li>Oxford</li></settlement><orgName><li>Université d'Oxford</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Jovcevski, Blagojce" sort="Jovcevski, Blagojce" uniqKey="Jovcevski B" first="Blagojce" last="Jovcevski">Blagojce Jovcevski</name></noRegion><name sortKey="Andrew Aquilina, J" sort="Andrew Aquilina, J" uniqKey="Andrew Aquilina J" first="J" last="Andrew Aquilina">J. Andrew Aquilina</name><name sortKey="Ecroyd, Heath" sort="Ecroyd, Heath" uniqKey="Ecroyd H" first="Heath" last="Ecroyd">Heath Ecroyd</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Benesch, Justin L P" sort="Benesch, Justin L P" uniqKey="Benesch J" first="Justin L P" last="Benesch">Justin L P. Benesch</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000777 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000777 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:29520626
|texte= The influence of the N-terminal region proximal to the core domain on the assembly and chaperone activity of αB-crystallin.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:29520626" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |