Self-assembly is important for TIP47 function in mannose 6-phosphate receptor transport

Paul M. Sincock, Ian G. Ganley, Jeffrey P. Krise, Sven Diederichs, Ulf Sivars, Brian O'Connor, Li Ding, Suzanne R. Pfeffer (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


TIP47 (tail-interacting protein of 47 kDa) binds to the cytoplasmic domains of mannose 6-phosphate receptors and is required for their transport from endosomes to the trans-Golgi network in vitro and in living cells. TIP47 occurs in cytosol as an oligomer; it chromatographs with an apparent mass of ∼300 kDa and displays an S-value of ∼13. Recombinant TIP47 forms homo-oligomers that are likely to represent hexamers, as determined by chemical cross-linking. Removal of TIP47 residues 1-151 yields a protein that behaves as a monomer upon gel filtration, yet is fully capable of binding mannose 6-phosphate receptor cytoplasmic domains. The presence of an oligomerization domain in the N-terminus of TIP47 was confirmed by expression of N-terminal residues 1-133 or 1-257 in mammalian cells. Co-expression of full-length TIP47 with either of these fragments led to the formation of higher-order aggregates of wild-type TIP47. Furthermore, the N-terminal domains expressed alone also occurred as oligomers. These studies reveal an N-terminal oligomerization domain in TIP47, and show that oligomerization is not required for TIP47 recognition of mannose 6-phosphate receptors. However, oligomerization is required for TIP47 stimulation of mannose 6-phosphate receptor transport from endosomes to the trans-Golgi in vivo.

Original languageEnglish
Pages (from-to)18-25
Number of pages8
Issue number1
Publication statusPublished - 1 Jan 2003


  • Endosome
  • Lysosome
  • Mannose 6-phosphate receptor
  • Membrane traffic
  • TIP47

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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