In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 34 ( 2020-08-25), p. 20794-20802
Kurzfassung:
Cis- prenyltransferase ( cis- PTase) catalyzes the rate-limiting step in the synthesis of glycosyl carrier lipids required for protein glycosylation in the lumen of endoplasmic reticulum. Here, we report the crystal structure of the human NgBR/DHDDS complex, which represents an atomic resolution structure for any heterodimeric cis -PTase. The crystal structure sheds light on how NgBR stabilizes DHDDS through dimerization, participates in the enzyme’s active site through its C-terminal -RXG- motif, and how phospholipids markedly stimulate cis -PTase activity. Comparison of NgBR/DHDDS with homodimeric cis -PTase structures leads to a model where the elongating isoprene chain extends beyond the enzyme’s active site tunnel, and an insert within the α3 helix helps to stabilize this energetically unfavorable state to enable long-chain synthesis to occur. These data provide unique insights into how heterodimeric cis -PTases have evolved from their ancestral, homodimeric forms to fulfill their function in long-chain polyprenol synthesis.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.2008381117
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2020
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12