6y38

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Crystal structure of Whirlin PDZ3 in complex with Myosin 15a C-terminal PDZ binding motif peptide

Structural highlights

6y38 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.697Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

WHRN_MOUSE Defects in Whrn are the cause of the phenotype whirler (wi). Mutants are characterized by deafness due to malformation of the cochlear inner and outer hair cells and by circling behavior. Stereocilia are shorter and wider than in wild-type animals and there is a decrease in the number of actin filaments in inner and outer hair cells. The number of outer hair cell stereocilia is reduced with increased spacing between them.[1] [2] [3]

Function

WHRN_MOUSE Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear.[4]

Publication Abstract from PubMed

Hearing is a mechanical and neurochemical process, which occurs in the hair cells of inner ear that converts the sound vibrations into electrical signals transmitted to the brain. The multi-PDZ scaffolding protein whirlin plays a critical role in the formation and function of stereocilia exposed at the surface of hair cells. In this article, we reported seven stereociliary proteins that encode PDZ binding motifs (PBM) and interact with whirlin PDZ3, where four of them are first reported. We solved the atomic resolution structures of complexes between whirlin PDZ3 and the PBMs of myosin 15a, CASK, harmonin a1 and taperin. Interestingly, the PBM of CASK and taperin are rare non-canonical PBM, that are not localized at the extreme C-terminus. This large capacity to accommodate various partners could be related to the distinct functions of whirlin at different stages of the hair cell development.

Deciphering the Unexpected Binding Capacity of the Third PDZ Domain of Whirlin to Various Cochlear Hair Cell Partners.,Zhu Y, Delhommel F, Cordier F, LUchow S, Mechaly A, Colcombet-Cazenave B, Girault V, Pepermans E, Bahloul A, Gautier C, Brule S, Raynal B, Hoos S, Haouz A, Caillet-Saguy C, Ivarsson Y, Wolff N J Mol Biol. 2020 Sep 21. pii: S0022-2836(20)30554-4. doi:, 10.1016/j.jmb.2020.09.012. PMID:32971111[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
1 reviews cite this structure
Liquid-liquid phase separation in hair cell stereocilia development and maintenance.
Li et al. (2023)
0 more
2 other articles
No citations found

References

  1. ↑ Holme RH, Kiernan BW, Brown SD, Steel KP. Elongation of hair cell stereocilia is defective in the mouse mutant whirler. J Comp Neurol. 2002 Aug 12;450(1):94-102. PMID:12124769 doi:http://dx.doi.org/10.1002/cne.10301
  2. ↑ Mburu P, Mustapha M, Varela A, Weil D, El-Amraoui A, Holme RH, Rump A, Hardisty RE, Blanchard S, Coimbra RS, Perfettini I, Parkinson N, Mallon AM, Glenister P, Rogers MJ, Paige AJ, Moir L, Clay J, Rosenthal A, Liu XZ, Blanco G, Steel KP, Petit C, Brown SD. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nat Genet. 2003 Aug;34(4):421-8. PMID:12833159 doi:10.1038/ng1208
  3. ↑ Mogensen MM, Rzadzinska A, Steel KP. The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development. Cell Motil Cytoskeleton. 2007 Jul;64(7):496-508. PMID:17326148 doi:http://dx.doi.org/10.1002/cm.20199
  4. ↑ Kikkawa Y, Mburu P, Morse S, Kominami R, Townsend S, Brown SD. Mutant analysis reveals whirlin as a dynamic organizer in the growing hair cell stereocilium. Hum Mol Genet. 2005 Feb 1;14(3):391-400. Epub 2004 Dec 8. PMID:15590699 doi:http://dx.doi.org/ddi035
  5. ↑ Zhu Y, Delhommel F, Cordier F, Lüchow S, Mechaly A, Colcombet-Cazenave B, Girault V, Pepermans E, Bahloul A, Gautier C, Brûlé S, Raynal B, Hoos S, Haouz A, Caillet-Saguy C, Ivarsson Y, Wolff N. Deciphering the Unexpected Binding Capacity of the Third PDZ Domain of Whirlin to Various Cochlear Hair Cell Partners. J Mol Biol. 2020 Nov 6;432(22):5920-5937. PMID:32971111 doi:10.1016/j.jmb.2020.09.012

Contents


PDB ID 6y38

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OCA

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