Lessons on protein structure from interleukin‐4: All disulfides are not created equal
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.8/8883 |
Resumo: | Funding information European Regional Development Fund; Fundaçao para a Ciência e a Tecnologia, ˜ Grant/Award Numbers: UIDB/00313/2020, UIDP/00313/2020; FEDER/COMPETE, Grant/Award Numbers: CENTRO07-CT62-FEDER-002012, RECI/QEQQFI/0168/2012; Rede Nacional de Ressonância Magnética Nuclear (RNRMN/ PTNMR); ALiCE, Grant/Award Number: LA/ P/0045/2020; LSRE-LCM, Grant/Award Numbers: UIDP/50020/2020, UIDB/50020/2020; FCT/MCTES (PIDDAC) |
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Lessons on protein structure from interleukin‐4: All disulfides are not created equalNMR relaxationDisulfide bondsFour-helix bundleInterleukin-4Molecular dynamicsSimulationsRDC-refined NMR solution structuresFunding information European Regional Development Fund; Fundaçao para a Ciência e a Tecnologia, ˜ Grant/Award Numbers: UIDB/00313/2020, UIDP/00313/2020; FEDER/COMPETE, Grant/Award Numbers: CENTRO07-CT62-FEDER-002012, RECI/QEQQFI/0168/2012; Rede Nacional de Ressonância Magnética Nuclear (RNRMN/ PTNMR); ALiCE, Grant/Award Number: LA/ P/0045/2020; LSRE-LCM, Grant/Award Numbers: UIDP/50020/2020, UIDB/50020/2020; FCT/MCTES (PIDDAC)Interleukin-4 (IL-4) is a hematopoietic cytokine composed by a four-helix bundle stabilized by an antiparallel beta-sheet and three disulfide bonds: Cys3-Cys127, Cys24-Cys65, and Cys46-Cys99. IL-4 is involved in several immune responses associated to infection, allergy, autoimmunity, and cancer. Besides its physiological relevance, IL-4 is often used as a “model” for protein design and engineering. Hence, to understand the role of each disulfide in the structure and dynamics of IL-4, we carried out several spectroscopic analyses (circular dichroism [CD], fluorescence, nuclear magnetic resonance [NMR]), and molecular dynamics (MD) simulations on wild-type IL-4 and four IL-4 disulfide mutants. All disulfide mutants showed loss of structure,altered interhelical angles, and looser core packings, showing that all disulfides are relevant for maintaining the overall fold and stability of the four-helix bundle motif, even at very low pH. In the absence of the disulfide connecting both protein termini Cys3-Cys127, C3T-IL4 showed a less packed protein core, loss of secondary structure ( 9%) and fast motions on the sub-nanosecond time scale (lower S2 order parameters and larger τc correlation time), especially at the two protein termini, loops, beginning of helix A and end of helix D. In the absence of Cys24-Cys65, C24T-IL4 presented shorter alpha-helices (14% loss in helical content), altered interhelical angles, less propensity to form the small anti-parallel beta-sheet and increased dynamics. Simultaneously deprived of two disulfides (Cys3-Cys127 and Cys24-Cys65), IL-4 formed a partially folded “molten globule” with high 8-anilino-1-naphtalenesulphonic acid-binding affinity and considerable loss of secondary structure (50%decrease), as shown by the far UV-CD, NMR, and MD data.WileyIC-OnlineVaz, Daniela C.Rodrigues, J. RuiLoureiro‐Ferreira, NunoMüller, Thomas D.Sebald, WalterRedfield, ChristinaBrito, Rui M. M.2023-11-02T17:36:36Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.8/8883engVaz DC, Rodrigues JR, Loureiro-Ferreira N, et al. Lessons on protein structure from interleukin-4: All disulfides are not created equal. Proteins. 2023;1‐17. doi:10.1002/prot.266110887-3585https://doi.org/10.1002/prot.266111097-0134metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-17T15:58:23Zoai:iconline.ipleiria.pt:10400.8/8883Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:51:30.455478Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| title |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| spellingShingle |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal Vaz, Daniela C. NMR relaxation Disulfide bonds Four-helix bundle Interleukin-4 Molecular dynamics Simulations RDC-refined NMR solution structures |
| title_short |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| title_full |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| title_fullStr |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| title_full_unstemmed |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| title_sort |
Lessons on protein structure from interleukin‐4: All disulfides are not created equal |
| author |
Vaz, Daniela C. |
| author_facet |
Vaz, Daniela C. Rodrigues, J. Rui Loureiro‐Ferreira, Nuno Müller, Thomas D. Sebald, Walter Redfield, Christina Brito, Rui M. M. |
| author_role |
author |
| author2 |
Rodrigues, J. Rui Loureiro‐Ferreira, Nuno Müller, Thomas D. Sebald, Walter Redfield, Christina Brito, Rui M. M. |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
IC-Online |
| dc.contributor.author.fl_str_mv |
Vaz, Daniela C. Rodrigues, J. Rui Loureiro‐Ferreira, Nuno Müller, Thomas D. Sebald, Walter Redfield, Christina Brito, Rui M. M. |
| dc.subject.por.fl_str_mv |
NMR relaxation Disulfide bonds Four-helix bundle Interleukin-4 Molecular dynamics Simulations RDC-refined NMR solution structures |
| topic |
NMR relaxation Disulfide bonds Four-helix bundle Interleukin-4 Molecular dynamics Simulations RDC-refined NMR solution structures |
| description |
Funding information European Regional Development Fund; Fundaçao para a Ciência e a Tecnologia, ˜ Grant/Award Numbers: UIDB/00313/2020, UIDP/00313/2020; FEDER/COMPETE, Grant/Award Numbers: CENTRO07-CT62-FEDER-002012, RECI/QEQQFI/0168/2012; Rede Nacional de Ressonância Magnética Nuclear (RNRMN/ PTNMR); ALiCE, Grant/Award Number: LA/ P/0045/2020; LSRE-LCM, Grant/Award Numbers: UIDP/50020/2020, UIDB/50020/2020; FCT/MCTES (PIDDAC) |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-11-02T17:36:36Z 2023 2023-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.8/8883 |
| url |
http://hdl.handle.net/10400.8/8883 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Vaz DC, Rodrigues JR, Loureiro-Ferreira N, et al. Lessons on protein structure from interleukin-4: All disulfides are not created equal. Proteins. 2023;1‐17. doi:10.1002/prot.26611 0887-3585 https://doi.org/10.1002/prot.26611 1097-0134 |
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metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
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Wiley |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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