Article
PCki=cTP−0os(∨CTki−0)in which Ti−0 is the vector between the coordinates of i structure and
the chosen reference 0 (4YBQ, in this case), and PCk is one of the major
principal component axes, which can classify and cluster structures,
and extract motion information and transition pathways from them^52 ,^53.
For the MFS ensemble, the first component alone captures about 65%
of the structural variation associated with the rocker switch, thus sepa-
rating the crystallographic structures along the transport cycle. The
angle between the sugar-porter tandem repeats was estimated as the
angle formed by TM2 and TM8, using an in-house Visual Molecular
Dynamics script.
Reporting summary
Further information on research design is available in the Nature
Research Reporting Summary linked to this paper.
Data availability
The coordinates and the structure factors for PfHT1 have been depos-
ited in the PDB 6RW3. All data are available in the paper or Supplemen-
tary Information.
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Acknowledgements We thank D. Daley for advice on PfHT1 overexpression optimization, and
G. von Heijne and S. Newstead for critical reading of the manuscript. X-ray diffraction data
were collected at the European Synchrotron Radiation Facility beamlines, the Diamond Light
Source beamlines and the MaxIV BioMax beamline with assistance from beamline scientists.
This work was funded by the Knut and Alice Wallenberg Foundation (D.D.) and, the Science for
Life Laboratory (L.D.); D.D. acknowledges support from EMBO through the Young Investigator
Program (YIP).
Author contributions D.D. designed the project. Cloning, expression screening and
crystallization of PfHT1 were carried out by A.A.Q. Data collection, structure determination and
refinement of PfHT1 were carried out by A.A.Q., E.N., J.B., R.M., M.C. and D.D. Experiments for
functional analysis were carried out by A.A.Q. and A.S. Molecular dynamics simulations of
PfHT1 were carried out by S.E.M. and L.D. Sugar porter PCA was carried out by L.O. The
manuscript was prepared by D.D. with contributions from all authors.
Competing interests The authors declare no competing interests.
Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-020-
1963-z.
Correspondence and requests for materials should be addressed to D.D.
Peer review information Nature thanks Jeff Abramson and the other, anonymous, reviewer(s)
for their contribution to the peer review of this work.
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