3SF4

Crystal structure of the complex between the conserved cell polarity proteins Inscuteable and LGN

Summary for 3SF4

• Entry DOI: 10.2210/pdb3sf4/pdb
• Descriptor: G-protein-signaling modulator 2, Protein inscuteable homolog (3 entities in total)
• Functional Keywords: tetratricopeptide repeat, tpr, cell polarity, asymmetric cell division, mitotic spindle orientation, cytoplasm and cell cortex, signaling protein-protein binding complex, signaling protein/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P81274 Q1MX18
• Total number of polymer chains: 6
• Total formula weight: 151637.23

Authors

Yuzawa, S.,Kamakura, S.,Iwakiri, Y.,Hayase, J.,Sumimoto, H. (deposition date: 2011-06-12, release date: 2011-11-23, Last modification date: 2023-11-01)

Primary citation

Yuzawa, S.,Kamakura, S.,Iwakiri, Y.,Hayase, J.,Sumimoto, H.
Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN)
Proc.Natl.Acad.Sci.USA, 108:19210-19215, 2011

PubMed Abstract: Interaction between the mammalian cell polarity proteins mInsc (mammalian homologue of Inscuteable) and Leu-Gly-Asn repeat-enriched protein (LGN), as well as that between their respective Drosophila homologues Inscuteable and Partner of Inscuteable (Pins), plays crucial roles in mitotic spindle orientation, a process contributing to asymmetric cell division. Here, we report a crystal structure of the LGN-binding domain (LBD) of human mInsc complexed with the N-terminal tetratricopeptide repeat (TPR) motifs of human LGN at 2.6-Å resolution. In the complex, mInsc-LBD adopts an elongated structure with three binding modules--an α-helix, an extended region, and a β-sheet connected with a loop--that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPRs. Structural analysis and structure-based mutagenesis define residues that are critical for mInsc-LGN association, and reveal that the activator of G-protein signaling 3 (AGS3)-binding protein Frmpd1 [4.1/ezrin/radixin/moesin (FERM) and PSD-95/Dlg/ZO-1 (PDZ) domain-containing protein 1] and its relative Frmpd4 interact with LGN via a region homologous to a part of mInsc-LBD, whereas nuclear mitotic apparatus protein (NuMA) and the C terminus of LGN recognize the TPR domain in a manner different from that by mInsc. mInsc binds to LGN with the highest affinity (K(D) ≈ 2.4 nM) and effectively replaces the Frmpd proteins, NuMA, and the LGN C terminus, suggesting the priority of mInsc in binding to LGN. We also demonstrate, using mutant proteins, that mInsc-LGN interaction is vital for stabilization of LGN and for intracellular localization of mInsc.

PubMed: 22074847
DOI: 10.1073/pnas.1110951108

Experimental method

X-RAY DIFFRACTION (2.6 Å)