6RW3

The molecular basis for sugar import in malaria parasites.

6RW3 の概要

• エントリーDOI: 10.2210/pdb6rw3/pdb
• 分子名称: Hexose transporter 1, alpha-D-glucopyranose, beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: transporter, membrane protein
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 224743.22

構造登録者

Qureshi, A.,Matsuoka, R.,Brock, J.,Drew, D. (登録日: 2019-06-03, 公開日: 2020-01-29, 最終更新日: 2024-01-24)

主引用文献

Qureshi, A.A.,Suades, A.,Matsuoka, R.,Brock, J.,McComas, S.E.,Nji, E.,Orellana, L.,Claesson, M.,Delemotte, L.,Drew, D.
The molecular basis for sugar import in malaria parasites.
Nature, 578:321-325, 2020

PubMed Abstract: Elucidating the mechanism of sugar import requires a molecular understanding of how transporters couple sugar binding and gating events. Whereas mammalian glucose transporters (GLUTs) are specialists, the hexose transporter from the malaria parasite Plasmodium falciparum PfHT1 has acquired the ability to transport both glucose and fructose sugars as efficiently as the dedicated glucose (GLUT3) and fructose (GLUT5) transporters. Here, to establish the molecular basis of sugar promiscuity in malaria parasites, we determined the crystal structure of PfHT1 in complex with D-glucose at a resolution of 3.6 Å. We found that the sugar-binding site in PfHT1 is very similar to those of the distantly related GLUT3 and GLUT5 structures. Nevertheless, engineered PfHT1 mutations made to match GLUT sugar-binding sites did not shift sugar preferences. The extracellular substrate-gating helix TM7b in PfHT1 was positioned in a fully occluded conformation, providing a unique glimpse into how sugar binding and gating are coupled. We determined that polar contacts between TM7b and TM1 (located about 15 Å from D-glucose) are just as critical for transport as the residues that directly coordinate D-glucose, which demonstrates a strong allosteric coupling between sugar binding and gating. We conclude that PfHT1 has achieved substrate promiscuity not by modifying its sugar-binding site, but instead by evolving substrate-gating dynamics.

PubMed: 31996846
DOI: 10.1038/s41586-020-1963-z

実験手法

X-RAY DIFFRACTION (3.65 Å)