PDBsum entry 1u39

Protein transport

PDB id: 1u39

Contents

Protein chain

80 a.a. *

* Residue conservation analysis

PDB id:

1u39

Name:

Protein transport

Title:

Auto-inhibition mechanism of x11s/mints family scaffold proteins revealed by the closed conformation of the tandem pdz domains

Structure:

Amyloid beta a4 precursor protein-binding, family a, member 1. Chain: a. Fragment: pdz2 domain. Synonym: x11alpha/mint1, phosphotyrosine-binding/-interacting domain (ptb)-bearing protein, neuronal munc18-1-interacting protein 1, neuron-specific x11 protein, adaptor protein x11alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

W.Feng,J.-F.Long,L.-N.Chan,C.He,A.Fu,J.Xia,N.Y.Ip,M.Zhang

Key ref:

J.F.Long et al. (2005). Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem. Nat Struct Mol Biol, 12, 722-728. PubMed id: 16007100 DOI: 10.1038/nsmb958

Date:

21-Jul-04 Release date: 26-Jul-05

Protein chain

Q02410  (APBA1_HUMAN) -  Amyloid-beta A4 precursor protein-binding family A member 1 from Homo sapiens

Seq: 837 a.a.

Struc: 80 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb958

Nat Struct Mol Biol 12:722-728 (2005)

PubMed id: 16007100

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

J.F.Long, W.Feng, R.Wang, L.N.Chan, F.C.Ip, J.Xia, N.Y.Ip, M.Zhang.

ABSTRACT

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.

Selected figure(s)

Figure 3.
Figure 3. Structures of the X11 PDZ domains determined by NMR spectroscopy. (a -c) Ribbon diagrams of representative NMR structures of PDZ1 (a), PDZ1 in complex with C-peptide (b) and PDZ2 (c). The C-peptide in b is shown as an explicit atomic model. (d) Comparison of the B/ B groove conformation in PDZ1 (orange) and PDZ2 of PSD-95 (purple). The two PDZ domains were superimposed on each other using their respective B strands. The axis of the B helix in each PDZ domain is indicated by a solid rod at the center of the helical cylinder. (e) Surface representation of the PDZ1 -C-peptide complex. PDZ1 is shown as a surface model, the backbone of the C-peptide is shown as a white worm, and the side chains of the last two residues of the C-peptide are shown as explicit atomic models. The hydrophobic residues of the surface model are shown in yellow, the positively charged residues in blue, the negatively charged residues in red and the rest of amino acids in gray.

Figure 6.
Figure 6. Correlation of the autoinhibited conformation of X11 with the target-binding property of the protein. The C termini of presenilin (DQLAFHQFYI) and calcium channel (HHPDQDHWC) were fused to glutathione S-transferase, respectively. Purified recombinant GST fusion proteins were used for binding assays with wild-type (WT) X11 and its various mutants, including Y836E, Y836F, PDZ1^* (PDZ1 deficient in ligand binding), PDZ2^* (PDZ2 deficient in ligand binding) and PDZ12^* (PDZ2 with both its ligand binding sites disrupted). The amount of X11 protein was detected by immunoblotting with antibody to c-Myc (9E10).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 722-728) copyright 2005.

Figures were selected by an automated process.