PXD031707

PXD031707 is an original dataset announced via ProteomeXchange.

Title	Structural analysis of human cis-prenyltransferase
Description	Isoprenoids are synthesized by the prenyltransferases superfamily, which is subdivided according to the product stereoisomerism and length. In short- and medium-chain isoprenoids, product length correlates with active site volume. However, enzymes synthesizing long-chain products and rubber synthases fail to conform to this paradigm, due to an unexpectedly small active site. Here, we focused on the human cis-prenyltransferase complex (hcis-PT), residing at the endoplasmic reticulum membrane and playing a crucial role in protein glycosylation. Crystallographic investigation of hcis-PT along the reaction cycle revealed an outlet for the elongating product. Hydrogen-deuterium exchange mass spectrometry analysis showed that the hydrophobic active site core is flanked by dynamic regions consistent with separate inlet and outlet orifices. Finally, using a fluorescence substrate analog, we show that product elongation and membrane association are closely correlated. Together, our results support direct membrane insertion of the elongating isoprenoid during catalysis, uncoupling active site volume from product length.
HostingRepository	PRIDE
AnnounceDate	2022-06-09
AnnouncementXML	Submission_2022-06-09_04:27:47.928.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petr Man
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics solarix series

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-16 02:47:05	ID requested
⏵ 1	2022-06-09 04:27:48	announced

Giladi M, Lisnyansky Bar-El M, Va, ň, kov, á P, Ferofontov A, Melvin E, Alkaderi S, Kavan D, Redko B, Haimov E, Wiener R, Man P, Haitin Y, -prenyltransferases. Sci Adv, 8(20):eabn1171(2022) [pubmed]

submitter keyword: cis-prenyltransferase, isoprenoid synthesis, H/D exchange mass spectrometry

Petr Man
contact affiliation	Laboratory of Structural Biology and Cell Signaling Institute of Microbiology of the Czech Acad Sci Prumyslova 595 252 50 Vestec Czech Republic
contact email	pman@biomed.cas.cz
lab head
Petr Man
contact affiliation	Institute of Microbiology of the CAS
contact email	pman@biomed.cas.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031707
     1. Label: PRIDE project
     2. Name: Structural analysis of human cis-prenyltransferase