Crystal Structures of a Complexed and Peptide-Free Membrane Protein–Binding Domain: Molecular Basis of Peptide Recognition by PDZ

Doyle, D.A.; Lee, Alice; Lewis, J. E.; Kim, Eunjoon; Sheng, Morgan; MacKinnon, Roderick

doi:10.1016/s0092-8674(00)81307-0

Cited by 1,094 publications

(1,379 citation statements)

References 35 publications

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“…For PDZ3 of hDlg a third a helix terminates the domain. Alignment of the sequences of the PDZ domains of the clones isolated in this study along with that of PDZ3 of PSD-95 shows that the most important variability occurs in the size of the loop separating strands bB and bC in agreement with previous observations (Figure 2) (Doyle et al, 1996).…”

Section: Binding Of Tax To Pdz Proteinssupporting

confidence: 91%

“…The structural data show that the terminal valine is engaged in a hydrophobic pocket¯anked by the b sheet B and the a helix B. A carboxylate binding loop of the PDZ domain which is located between the b sheets A and B form a cradle of amide nitrogens which establish hydrogen bonds with this terminal valine (Doyle et al, 1996). The residues involved in these bonds are well conserved among the di erent clones presented here.…”

Section: Interaction Of the Viral Protein Tax With Pdz Proteinsmentioning

confidence: 74%

“…the carboxy-terminal valine and the threonine at position 72. The resolution of the structure of a complex associating PDZ3 of PSD-95 and a peptide has determined the molecular basis of such interactions (Doyle et al, 1996). These ®ndings have been also supported by a recent study of the motifs interacting with various PDZ domains by the oriented peptide library technique (Songyang et al, 1997).…”

Section: Interaction Of the Viral Protein Tax With Pdz Proteinsmentioning

confidence: 81%

“…Clones 2 and 40 code for larger proteins including a single PDZ domain. The three dimensional structures of the PDZ3 domains of PSD-95 and of hDlg have been determined and both correspond to six b sheets (bA to bF) and two a helices Doyle et al, 1996). For PDZ3 of hDlg a third a helix terminates the domain.…”

Section: Binding Of Tax To Pdz Proteinsmentioning

confidence: 99%

“…The dots above the alignment correspond to identities and the vertical bars to conservative changes. The six b sheets (white bars, bA to bF) and the two a helices (black bars, aA and aB) present in the structure of the PDZ3 motif of PSD-95 (Doyle et al, 1996) These experiments were done by examining the coloration of the colonies in a ®lter assay. This technique is more sensitive than the liquid culture assay previously presented, but does not allow precise comparison of intense b-galactosidase activities.…”

Section: Mapping Of the Domains Of Tax Mediating Interaction With Thementioning

confidence: 99%

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The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

et al. 1998

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Infection by HTLV-1 has been correlated with the appearance of various proliferative or degenerative diseases. Some of these disorders have been observed in transgenic mice expressing the Tax protein, which is known to transactivate various viral and cellular promoters through interactions with several transcription factors. In this study we show that the C-terminus of this viral oncoprotein represents a motif permitting binding of Tax to the PDZ domains of several cellular proteins. A two-hybrid screen with Tax as bait indeed yielded complementary DNAs coding for six proteins including PDZ domains. Two of them correspond to truncated forms of the PSD-95 and b1-syntrophin proteins, another clone codes for a protein homologous to the product of the C. elegans gene lin-7. The other three clones code for new human members of the PDZ family of cellular proteins. The interaction of Tax with the products of these clones was con®rmed by immunoprecipitation assays in mammalian cells, and analysis of various mutants of Tax established the importance of the Cterminal amino acids for several of these interactions. These data suggest that Tax could perturb the normal function of targeted cellular proteins by strongly interacting with their PDZ domains.

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Section: Binding Of Tax To Pdz Proteinssupporting

confidence: 91%

Section: Interaction Of the Viral Protein Tax With Pdz Proteinsmentioning

confidence: 74%

Section: Interaction Of the Viral Protein Tax With Pdz Proteinsmentioning

confidence: 81%

Section: Binding Of Tax To Pdz Proteinsmentioning

confidence: 99%

Section: Mapping Of the Domains Of Tax Mediating Interaction With Thementioning

confidence: 99%

See 3 more Smart Citations

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

et al. 1998

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Drosophila larval neuromuscular junction: Molecular components and mechanisms underlying synaptic plasticity

Koh

Gramates

Budnik

2000

Microsc. Res. Tech.

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Understanding the mechanisms that mediate synaptic plasticity is a primary goal of molecular neuroscience. The Drosophila larval neuromuscular junction provides a particularly useful model for investigating the roles of synaptic components in both structural and functional plasticity. The powerful molecular genetics of this system makes it possible to uncover new synaptic components and signaling molecules, as well as their function in the intact organism. Together with the mouse hippocampus and Aplysia dissociated cell culture, the Drosophila larval neuromuscular junction has been among the most valuable model systems for examining the molecular and cellular basis of neuronal plasticity. Microsc. Res. Tech. 49:14–25, 2000. © 2000 Wiley‐Liss, Inc.

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A phosphoinositide-binding sequence is shared by PH domain target molecules—a model for the binding of PH domains to proteins

Alberti

1998

Proteins

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Pleckstrin homology (PH) domains have been proven to bind phosphoinositides (PI) and inositolphosphates (IP). On the other hand, a binding of PH domains to proteins is still a matter of debate. The goal of this work was to identify potential PH domain protein target sites and to build a model for PH domain-protein binding. A candidate sequence, called HIKE, was identified by sequence homology analysis of the proteins that are considered the strongest PH binding candidates, i.e., Gbeta, PKC, and Akt. HIKE contains a PI binding sequence and fulfills several criteria for a potential PH-binding site, i.e., it is present in other PH-binding candidates, lies in regulatory regions independently predicted to bind PH domains, and is conserved in 3-D structure among different molecules. These findings and the similarities with the mode of binding of PTB and PDZ domains suggest a beta strand-beta strand coordination model for PH-protein binding. The HIKE model predicts that membrane anchoring of PH domains and their targets could be a critical step in their interaction, which would consistently explain why PH-protein binding has only been detected in the presence of PI.

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Crystal Structures of a Complexed and Peptide-Free Membrane Protein–Binding Domain: Molecular Basis of Peptide Recognition by PDZ

Cited by 1,094 publications

References 35 publications

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

Drosophila larval neuromuscular junction: Molecular components and mechanisms underlying synaptic plasticity

A phosphoinositide-binding sequence is shared by PH domain target molecules—a model for the binding of PH domains to proteins

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