Article abstract


Nature Structural & Molecular Biology 12, 722 - 728 (2005)
Published online: 10 July 2005 | doi:10.1038/nsmb958

Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem

Jia-Fu Long1,2, Wei Feng1,2, Rui Wang1, Ling-Nga Chan1, Fanny C F Ip1, Jun Xia1, Nancy Y Ip1 & Mingjie Zhang1


Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conserved C-terminal tail of X11alpha folds back and inserts into the target-binding groove of the first PDZ domain. The binding of this tail occludes the binding of other target peptides. This autoinhibited conformation of X11 requires that the two PDZ domains and the entire C-terminal tail be covalently connected to form an integral structural unit. The autoinhibited conformation of the X11 PDZ tandem provides a mechanistic explanation for the unique target-binding properties of the protein and hints at potential regulatory mechanisms for the X11–target interactions.

Top
  1. Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
  2. These authors contributed equally to this work.

Correspondence to: Mingjie Zhang1 e-mail: mzhang@ust.hk



MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

Scaffold proteins as dynamic switches

Nature Chemical Biology News and Views (01 Dec 2007)

Love it or cleave it: Tough choices in protein quality control

Nature Structural Biology News and Views (01 Jun 2002)

RESEARCH

Metabolomic study of cisplatin-induced nephrotoxicity

Kidney International Original Article

Surrogate Endpoints for the Treatment of Venous Leg Ulcers

Journal of Investigative Dermatology Original Article

See all 51 matches for Research