4A1S

Crystallographic structure of the Pins:Insc complex

Summary for 4A1S

• Entry DOI: 10.2210/pdb4a1s/pdb
• Descriptor: PARTNER OF INSCUTEABLE, RE60102P (3 entities in total)
• Functional Keywords: cell cycle, lgn, mitotic spindle orientation, asymmetric cell divisions
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY); More
• Total number of polymer chains: 4
• Total formula weight: 96880.58

Authors

Culurgioni, S.,Alfieri, A.,Pendolino, V.,Laddomada, F.,Mapelli, M. (deposition date: 2011-09-19, release date: 2012-03-28, Last modification date: 2024-05-08)

Primary citation

Culurgioni, S.,Alfieri, A.,Pendolino, V.,Laddomada, F.,Mapelli, M.
Inscuteable and Numa Proteins Bind Competitively to Leu-Gly- Asn Repeat-Enriched Protein (Lgn) During Asymmetric Cell Divisions.
Proc.Natl.Acad.Sci.USA, 108:20998-, 2011

PubMed Abstract: Coupling of spindle orientation to cellular polarity is a prerequisite for epithelial asymmetric cell divisions. The current view posits that the adaptor Inscuteable (Insc) bridges between Par3 and the spindle tethering machinery assembled on NuMALGNGαi(GDP), thus triggering apico-basal spindle orientation. The crystal structure of the Drosophila ortholog of LGN (known as Pins) in complex with Insc reveals a modular interface contributed by evolutionary conserved residues. The structure also identifies a positively charged patch of LGN binding to an invariant EPE-motif present on both Insc and NuMA. In vitro competition assays indicate that Insc competes with NuMA for LGN binding, displaying a higher affinity, and that it is capable of opening the LGN conformational switch. The finding that Insc and NuMA are mutually exclusive interactors of LGN challenges the established model of force generators assembly, which we revise on the basis of the newly discovered biochemical properties of the intervening components.

PubMed: 22171003
DOI: 10.1073/PNAS.1113077108

Experimental method

X-RAY DIFFRACTION (2.1 Å)