4wnd | pdb_00004wnd
Crystal structure of the TPR domain of LGN in complex with Frmpd4/Preso1 at 1.5 Angstrom resolution
Structural highlights
Disease[GPSM2_HUMAN] Autosomal recessive nonsyndromic sensorineural deafness type DFNB;Chudley-McCullough syndrome. Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] [2] [FRPD4_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function[GPSM2_HUMAN] Plays an important role in spindle pole orientation. Interacts and contributes to the functional activity of G(i) alpha proteins. Acts to stabilize the apical complex during neuroblast divisions.[3] [FRPD4_HUMAN] Positive regulator of dendritic spine morphogenesis and density. Required for the maintenance of excitatory synaptic transmission. Binds phosphatidylinositol 4,5-bisphosphate.[4] Publication Abstract from PubMedThe 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 A 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)XEX4-5(E/D/Q)X1-2(K/R)X0-1(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 alpha-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. Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN.,Takayanagi H, Yuzawa S, Sumimoto H Acta Crystallogr F Struct Biol Commun. 2015 Feb;71(Pt 2):175-83. doi:, 10.1107/S2053230X14028143. Epub 2015 Jan 28. PMID:25664792[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||
