6KYL

Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 in Complex with (2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate

Replaces:  5JQO

Summary for 6KYL

• Entry DOI: 10.2210/pdb6kyl/pdb
• Descriptor: Mitochondrial distribution and morphology protein 35, Protein UPS1, mitochondrial, (2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate (3 entities in total)
• Functional Keywords: lipid transport, transport protein
• Biological source: Saccharomyces cerevisiae S288c (Yeast); More
• Total number of polymer chains: 4
• Total formula weight: 63695.97

Authors

Lu, J.,Chan, K.C.,Zhai, Y.,Fan, J.,Sun, F. (deposition date: 2019-09-19, release date: 2019-10-02, Last modification date: 2024-10-23)

Primary citation

Lu, J.,Chan, C.,Yu, L.,Fan, J.,Sun, F.,Zhai, Y.
Molecular mechanism of mitochondrial phosphatidate transfer by Ups1.
Commun Biol, 3:468-468, 2020

PubMed Abstract: Cardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The α2-loop, L2-loop, and α3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.

PubMed: 32843686
DOI: 10.1038/s42003-020-01121-x

Experimental method

X-RAY DIFFRACTION (3.55 Å)