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Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN
Author(s) -
Takayanagi Hiroki,
Yuzawa Satoru,
Sumimoto Hideki
Publication year - 2015
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x14028143
Subject(s) - tetratricopeptide , antiparallel (mathematics) , superhelix , signal transducing adaptor protein , chemistry , crystallography , physics , biochemistry , signal transduction , dna , dna replication , quantum mechanics , magnetic field , dna supercoil , gene
The adaptor protein LGN interacts via the N‐terminal domain comprising eight tetratricopeptide‐repeat (TPR) motifs with its partner proteins mInsc, NuMA, Frmpd1 and Frmpd4 in a mutually exclusive manner. Here, the crystal structure of the LGN TPR domain in complex with human Frmpd4 is described at 1.5 Å resolution. In the complex, the LGN‐binding region of Frmpd4 (amino‐acid residues 990–1011) adopts an extended structure that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPR motifs. Comparison with the previously determined structures of the LGN–Frmpd1, LGN–mInsc and LGN–NuMA complexes reveals that these partner proteins interact with LGN TPR1–6 via a common core binding region with consensus sequence (E/Q) X E X 4–5 (E/D/Q) X 1–2 (K/R) X 0–1 (V/I). In contrast to Frmpd1, Frmpd4 makes additional contacts with LGN via regions N‐ and C‐terminal to the core sequence. The N‐terminal extension is replaced by a specific α‐helix in mInsc, which drastically increases the direct contacts with LGN TPR7/8, consistent with the higher affinity of mInsc for LGN. A crystal structure of Frmpd4‐bound LGN in an oxidized form is also reported, although oxidation does not appear to strongly affect the interaction with Frmpd4.