4JHR: An Auto-inhibited Conformation Of Lgn Reveals A Distinct Interaction Mode Between Goloco Motifs And Tpr Motifs

LGN plays essential roles in asymmetric cell divisions via its N-terminal TPR-motif-mediated binding to mInsc and NuMA. This scaffolding activity requires the release of the autoinhibited conformation of LGN by binding of Galpha(i) to its C-terminal GoLoco (GL) motifs. The interaction between the GL and TPR motifs of LGN represents a distinct GL/target binding mode with an unknown mechanism. Here, we show that two consecutive GL motifs of LGN form a minimal TPR-motif-binding unit. GL12 and GL34 bind to TPR0-3 and TPR4-7, respectively. The crystal structure of a truncated LGN reveals that GL34 forms a pair of parallel alpha helices and binds to the concave surface of TPR4-7, thereby preventing LGN from binding to other targets. Importantly, the GLs bind to TPR motifs with a mode distinct from that observed in the GL/Galpha(i).GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.
PDB ID: 4JHRDownload
MMDB ID: 110731
PDB Deposition Date: 2013/3/5
Updated in MMDB: 2013/09
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4JHR: dimeric; determined by author and by software (PISA)
Molecular Components in 4JHR
Label Count Molecule
Proteins (2 molecules)
G-protein-signaling Modulator 2(Gene symbol: Gpsm2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB