Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication
Identifieur interne : 000031 ( Main/Exploration ); précédent : 000030; suivant : 000032Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication
Auteurs : Joane K. Rustiguel [Brésil] ; Ricardo O. S. Soares [Brésil] ; Steve P. Meisburger [États-Unis] ; Katherine M. Davis [États-Unis] ; Kristina L. Malzbender [États-Unis] ; Nozomi Ando [États-Unis] ; Marcelo Dias-Baruffi [Brésil] ; Maria Cristina Nonato [Brésil]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive. Here, we investigate galectin-4 using X-ray crystallography, small- and wide-angle X-ray scattering, molecular modelling, molecular dynamics simulations, and differential scanning fluorimetry assays and describe for the first time a structural model for human galectin-4. Our results provide insight into the structural role of the linker-peptide and shed light on the dynamic characteristics of the mechanism of carbohydrate recognition among tandem-repeat galectins.
Url:
DOI: 10.1038/srep33633
PubMed: 27642006
PubMed Central: 5027518
Affiliations:
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Rustiguel</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo</institution>, SP,<country>Brazil</country></nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Soares, Ricardo O S" sort="Soares, Ricardo O S" uniqKey="Soares R" first="Ricardo O. S." last="Soares">Ricardo O. S. Soares</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo</institution>, SP,<country>Brazil</country></nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meisburger, Steve P" sort="Meisburger, Steve P" uniqKey="Meisburger S" first="Steve P." last="Meisburger">Steve P. Meisburger</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Chemistry, Princeton University</institution>, Princeton, NJ,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Davis, Katherine M" sort="Davis, Katherine M" uniqKey="Davis K" first="Katherine M." last="Davis">Katherine M. Davis</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Chemistry, Princeton University</institution>, Princeton, NJ,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Malzbender, Kristina L" sort="Malzbender, Kristina L" uniqKey="Malzbender K" first="Kristina L." last="Malzbender">Kristina L. Malzbender</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Chemistry, Princeton University</institution>, Princeton, NJ,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ando, Nozomi" sort="Ando, Nozomi" uniqKey="Ando N" first="Nozomi" last="Ando">Nozomi Ando</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Chemistry, Princeton University</institution>, Princeton, NJ,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dias Baruffi, Marcelo" sort="Dias Baruffi, Marcelo" uniqKey="Dias Baruffi M" first="Marcelo" last="Dias-Baruffi">Marcelo Dias-Baruffi</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo</institution>, SP,<country>Brazil</country></nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nonato, Maria Cristina" sort="Nonato, Maria Cristina" uniqKey="Nonato M" first="Maria Cristina" last="Nonato">Maria Cristina Nonato</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo</institution>, SP,<country>Brazil</country></nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive. Here, we investigate galectin-4 using X-ray crystallography, small- and wide-angle X-ray scattering, molecular modelling, molecular dynamics simulations, and differential scanning fluorimetry assays and describe for the first time a structural model for human galectin-4. Our results provide insight into the structural role of the linker-peptide and shed light on the dynamic characteristics of the mechanism of carbohydrate recognition among tandem-repeat galectins.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Barondes, S H" uniqKey="Barondes S">S. H. Barondes</name></author><author><name sortKey="Cooper, D N" uniqKey="Cooper D">D. N. Cooper</name></author><author><name sortKey="Gitt, M A" uniqKey="Gitt M">M. A. Gitt</name></author><author><name sortKey="Leffler, H" uniqKey="Leffler H">H. Leffler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hughes, R C" uniqKey="Hughes R">R. C. Hughes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leffler, H" uniqKey="Leffler H">H. Leffler</name></author><author><name sortKey="Carlsson, S" uniqKey="Carlsson S">S. 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Volkov</name></author><author><name sortKey="Svergun, D I" uniqKey="Svergun D">D. I. Svergun</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Brésil</li><li>États-Unis</li></country></list><tree><country name="Brésil"><noRegion><name sortKey="Rustiguel, Joane K" sort="Rustiguel, Joane K" uniqKey="Rustiguel J" first="Joane K." last="Rustiguel">Joane K. Rustiguel</name></noRegion><name sortKey="Dias Baruffi, Marcelo" sort="Dias Baruffi, Marcelo" uniqKey="Dias Baruffi M" first="Marcelo" last="Dias-Baruffi">Marcelo Dias-Baruffi</name><name sortKey="Nonato, Maria Cristina" sort="Nonato, Maria Cristina" uniqKey="Nonato M" first="Maria Cristina" last="Nonato">Maria Cristina Nonato</name><name sortKey="Soares, Ricardo O S" sort="Soares, Ricardo O S" uniqKey="Soares R" first="Ricardo O. S." last="Soares">Ricardo O. S. Soares</name></country><country name="États-Unis"><noRegion><name sortKey="Meisburger, Steve P" sort="Meisburger, Steve P" uniqKey="Meisburger S" first="Steve P." last="Meisburger">Steve P. Meisburger</name></noRegion><name sortKey="Ando, Nozomi" sort="Ando, Nozomi" uniqKey="Ando N" first="Nozomi" last="Ando">Nozomi Ando</name><name sortKey="Davis, Katherine M" sort="Davis, Katherine M" uniqKey="Davis K" first="Katherine M." last="Davis">Katherine M. Davis</name><name sortKey="Malzbender, Kristina L" sort="Malzbender, Kristina L" uniqKey="Malzbender K" first="Kristina L." last="Malzbender">Kristina L. Malzbender</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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