A duplicated motif controls assembly of zona pellucida domain proteins

Luca Jovine, Huayu Qi, Zev Williams, Eveline S. Litscher, Paul M. Wassarman

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Many secreted eukaryotic glycoproteins that play fundamental roles in development, hearing, immunity, and cancer polymerize into filaments and extracellular matrices through zona pellucida (ZP) domains. ZP domain proteins are synthesized as precursors containing C-terminal propeptides that are cleaved at conserved sites. However, the consequences of this processing and the mechanism by which nascent proteins assemble are unclear. By microinjection of mutated DNA constructs into growing oocytes and mammalian cell transfection, we have identified a conserved duplicated motif [EHP (external hydrophobic patch)/IHP (internal hydrophobic patch)] regulating the assembly of mouse ZP proteins. Whereas the transmembrane domain (TMD) of ZP3 can be functionally replaced by an unrelated TMD, mutations in either EHP or IHP do not hinder secretion of full-length ZP3 but completely abolish its assembly. Because mutants truncated before the TMD are not processed, we conclude that the conserved TMD of mammalian ZP proteins does not engage them in specific interactions but is essential for C-terminal processing. Cleavage of ZP precursors results in loss of the EHP, thereby activating secreted polypeptides to assemble by using the IHP within the ZP domain. Taken together, these findings suggest a general mechanism for assembly of ZP domain proteins.

Original languageEnglish (US)
Pages (from-to)5922-5927
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number16
DOIs
StatePublished - Apr 20 2004
Externally publishedYes

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Zona Pellucida
Proteins
Microinjections
Protein Domains
Hearing
Oocytes
Extracellular Matrix
Transfection
Immunity
Glycoproteins
Peptides
Mutation
DNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A duplicated motif controls assembly of zona pellucida domain proteins. / Jovine, Luca; Qi, Huayu; Williams, Zev; Litscher, Eveline S.; Wassarman, Paul M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 16, 20.04.2004, p. 5922-5927.

Research output: Contribution to journalArticle

Jovine, Luca ; Qi, Huayu ; Williams, Zev ; Litscher, Eveline S. ; Wassarman, Paul M. / A duplicated motif controls assembly of zona pellucida domain proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 16. pp. 5922-5927.
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