4ZWC

Crystal structure of maltose-bound human GLUT3 in the outward-open conformation at 2.6 angstrom

4ZWC の概要

• エントリーDOI: 10.2210/pdb4zwc/pdb
• 関連するPDBエントリー: 4ZW9 4ZWB
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Solute carrier family 2, facilitated glucose transporter member 3, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• 機能のキーワード: transporter, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114703.20

構造登録者

Deng, D.,Sun, P.C.,Yan, C.Y.,Yan, N. (登録日: 2015-05-19, 公開日: 2015-07-22, 最終更新日: 2023-11-08)

主引用文献

Deng, D.,Sun, P.C.,Yan, C.Y.,Ke, M.,Jiang, X.,Xiong, L.,Ren, W.,Hirata, K.,Yamamoto, M.,Fan, S.,Yan, N.
Molecular basis of ligand recognition and transport by glucose transporters
Nature, 526:391-396, 2015

PubMed Abstract: The major facilitator superfamily glucose transporters, exemplified by human GLUT1-4, have been central to the study of solute transport. Using lipidic cubic phase crystallization and microfocus X-ray diffraction, we determined the structure of human GLUT3 in complex with D-glucose at 1.5 Å resolution in an outward-occluded conformation. The high-resolution structure allows discrimination of both α- and β-anomers of D-glucose. Two additional structures of GLUT3 bound to the exofacial inhibitor maltose were obtained at 2.6 Å in the outward-open and 2.4 Å in the outward-occluded states. In all three structures, the ligands are predominantly coordinated by polar residues from the carboxy terminal domain. Conformational transition from outward-open to outward-occluded entails a prominent local rearrangement of the extracellular part of transmembrane segment TM7. Comparison of the outward-facing GLUT3 structures with the inward-open GLUT1 provides insights into the alternating access cycle for GLUTs, whereby the C-terminal domain provides the primary substrate-binding site and the amino-terminal domain undergoes rigid-body rotation with respect to the C-terminal domain. Our studies provide an important framework for the mechanistic and kinetic understanding of GLUTs and shed light on structure-guided ligand design.

PubMed: 26176916
DOI: 10.1038/nature14655

実験手法

X-RAY DIFFRACTION (2.6 Å)