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Evolutionary balance between foldability and functionality of a glucose transporter.
Choi, Hyun-Kyu; Kang, Hyunook; Lee, Chanwoo; Kim, Hyun Gyu; Phillips, Ben P; Park, Soohyung; Tumescheit, Charlotte; Kim, Sang Ah; Lee, Hansol; Roh, Soung-Hun; Hong, Heedeok; Steinegger, Martin; Im, Wonpil; Miller, Elizabeth A; Choi, Hee-Jung; Yoon, Tae-Young.
Afiliação
  • Choi HK; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Kang H; Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
  • Lee C; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Kim HG; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Phillips BP; Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
  • Park S; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Tumescheit C; Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
  • Kim SA; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK.
  • Lee H; Departments of Biological Sciences and Chemistry, Lehigh University, Bethlehem, PA, USA.
  • Roh SH; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Hong H; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Steinegger M; Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
  • Im W; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Miller EA; Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
  • Choi HJ; School of Biological Sciences, Seoul National University, Seoul, South Korea.
  • Yoon TY; Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
Nat Chem Biol ; 18(7): 713-723, 2022 07.
Article em En | MEDLINE | ID: mdl-35484435
Despite advances in resolving the structures of multi-pass membrane proteins, little is known about the native folding pathways of these complex structures. Using single-molecule magnetic tweezers, we here report a folding pathway of purified human glucose transporter 3 (GLUT3) reconstituted within synthetic lipid bilayers. The N-terminal major facilitator superfamily (MFS) fold strictly forms first, serving as a structural template for its C-terminal counterpart. We found polar residues comprising the conduit for glucose molecules present major folding challenges. The endoplasmic reticulum membrane protein complex facilitates insertion of these hydrophilic transmembrane helices, thrusting GLUT3's microstate sampling toward folded structures. Final assembly between the N- and C-terminal MFS folds depends on specific lipids that ease desolvation of the lipid shells surrounding the domain interfaces. Sequence analysis suggests that this asymmetric folding propensity across the N- and C-terminal MFS folds prevails for metazoan sugar porters, revealing evolutionary conflicts between foldability and functionality faced by many multi-pass membrane proteins.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Facilitadoras de Transporte de Glucose / Bicamadas Lipídicas Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Facilitadoras de Transporte de Glucose / Bicamadas Lipídicas Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article