한빛사논문
Hyun-Kyu Choi 1,2,6, Hyunook Kang 1,6, Chanwoo Lee 1,2,6, Hyun Gyu Kim1,2, Ben P. Phillips 3, Soohyung Park 4, Charlotte Tumescheit 1, Sang Ah Kim1,2, Hansol Lee 1,2, Soung-Hun Roh1,2, Heedeok Hong 5, Martin Steinegger1, Wonpil Im 4, Elizabeth A. Miller 3,*, Hee-Jung Choi 1,* and Tae-Young Yoon 1,2,*
1School of Biological Sciences, Seoul National University, Seoul, South Korea. 2Institute for Molecular Biology and Genetics, Seoul National University, Seoul, South Korea. 3Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK. 4Departments of Biological Sciences and Chemistry, Lehigh University, Bethlehem, PA, USA. 5Department of Chemistry and Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, USA. 6These authors contributed equally: Hyun-Kyu Choi, Hyunook Kang, Chanwoo Lee.
*Corresponding author.
Abstract
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.
논문정보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기