Structure and interaction of ubiquitin-associated domain of human Fas-associated factor 1

Jin Sue Song, Kyu Park Joon, Jae Jin Lee, Yun Seok Choi, Kyoung Seok Ryu, Jae Hong Kim, Eunhee Kim, Kong Joo Lee, Young Ho Jeon, Eunice Eun Kyong Kim

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20 Citations (Scopus)

Abstract

Fas-associated factor (FAF)-1 is a multidomain protein that was first identified as a member of the Fas death-inducing signaling complex, but later found to be involved in various biological processes. Although the exact mechanisms are not clear, FAF1 seems to play an important role in cancer, asbestos-induced mesotheliomas, and Parkinson's disease. It interacts with polyubiquitinated proteins, Hsp70, and p97/VCP (valosin-containing protein), in addition to the proteins of the Fas-signaling pathway. We have determined the crystal structure of the ubiquitin-associated domain of human FAF1 (hFAF1-UBA) and examined its interaction with ubiquitin and ubiquitin-like proteins using nuclear magnetic resonance. hFAF1-UBA revealed a canonical three-helical bundle that selectively binds to mono- and di-ubiquitin (Lys48-linked), but not to SUMO-1 (small ubiquitin-related modifier 1) or NEDD8 (neural precursor cell expressed, developmentally down-regulated 8). The interaction between hFAF1-UBA and di-ubiquitin involves hydrophobic interaction accompanied by a transition in the di-ubiquitin conformation. These results provide structural insight into the mechanism of polyubiquitin recognition by hFAF1-UBA. Published by Wiley-Blackwell.

Original languageEnglish
Pages (from-to)2265-2276
Number of pages12
JournalProtein Science
Volume18
Issue number11
DOIs
Publication statusPublished - 2009 Nov

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Song, J. S., Joon, K. P., Lee, J. J., Choi, Y. S., Ryu, K. S., Kim, J. H., Kim, E., Lee, K. J., Jeon, Y. H., & Kim, E. E. K. (2009). Structure and interaction of ubiquitin-associated domain of human Fas-associated factor 1. Protein Science, 18(11), 2265-2276. https://doi.org/10.1002/pro.237