Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide

Macias, María J.; Hyvönen, Marko; Baraldi, Elena; Schultz, Johan; Sudol, Marius; Saraste, Matti; Oschkinat, Hartmut

doi:10.1038/382646a0

Cited by 426 publications

(503 citation statements)

References 22 publications

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“…1C). These values are in good agreement with the K D values determined for Group I WW domains using various techniques including isothermal titration microcalorimetry (31,32). Considering these results, the problem of avidity was well avoided in the present measurement system.…”

Section: Spr Binding Assay Of Ww Domains Previouslysupporting

confidence: 77%

Common Mechanism of Ligand Recognition by Group II/III WW Domains

Kato

Nagata

Takahashi

et al. 2004

Journal of Biological Chemistry

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WW domain is a well known protein module that mediates protein to protein interactions by binding to proline-containing ligands. Based on the ligand predilections, the WW domains have been classified into four major groups. Group II and III WW domains have been reported to bind the proline-leucine and proline-arginine motifs, respectively. In the present study, using surface plasmon resonance technique we have shown that these WW domains have almost indistinguishable ligand preferences and kinetic properties. Hence, we propose that Group II and III WW domains should be joined together as one group (Group II/III). Unlike Group I and IV WW domains, Group II/III WW domains can bind simple polyprolines as well as the proline-leucine and proline-arginine motifs, and they possess two Xaa-proline (where Xaa is any amino acid) binding grooves similar to SH3 domains. Our work assigns Group II and III WW domains to a larger family of polyproline-binding modules and proteins, which includes SH3 domains and profilin. Because polyprolines belong to the most frequently found peptide motifs in several genomes, our study implies the versatile importance of Group II/III WW domains in signaling.

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Section: Spr Binding Assay Of Ww Domains Previouslysupporting

confidence: 77%

Common Mechanism of Ligand Recognition by Group II/III WW Domains

Kato

Nagata

Takahashi

et al. 2004

Journal of Biological Chemistry

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“…The WW domain is one of the smallest protein modules. Its 40 amino acids form a compact triple-stranded, antiparallel ␤ sheet (33). The two highly conserved tryptophan (W) residues are spaced 20 -22 amino acids apart and play an important role in its structure and function.…”

Section: Discussionmentioning

confidence: 99%

Atrophin-1-interacting Protein 4/Human Itch Is a Ubiquitin E3 Ligase for Human Enhancer of Filamentation 1 in Transforming Growth Factor-β Signaling Pathways

Guedes

Wang

2004

Journal of Biological Chemistry

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Atrophin-1-interacting protein 4 (AIP4) is the human homolog of the mouse Itch protein (hItch), an E3 ligase for Notch and JunB. Human enhancer of filamentation 1 (HEF1) has been implicated in signaling pathways such as those mediated by integrin, T cell receptor, and B cell receptor and functions as a multidomain docking protein. Recent studies suggest that HEF1 is also involved in the transforming growth factor-␤ (TGF-␤) signaling pathways, by interacting with Smad3, a key signal transducer downstream of the TGF-␤ type I receptor. The interaction of Smad3 with HEF1 induces HEF1 proteasomal degradation, which was further enhanced by TGF-␤ stimulation. The detailed molecular mechanisms of HEF1 degradation regulated by Smad3 were poorly understood. Here we report our studies that demonstrate the function of AIP4 as an ubiquitin E3 ligase for HEF1. AIP4 forms a complex with both Smad3 and HEF1 through its WW domains in a TGF-␤-independent manner and regulates HEF1 ubiquitination and degradation, which can be enhanced by TGF-␤ stimulation. These findings reveal a new mechanism for Smad3-regulated proteasomal degradation events and also broaden the network of cross-talk between the TGF-␤ signaling pathway and those involving HEF1 and AIP4.The transforming growth factor-␤ (TGF-␤) 1 signaling is involved in a broad range of cellular functions, including proliferation, adhesion, apoptosis, differentiation, and specification of developmental fate (1, 2). The extracellular signals were transduced to the nucleus by the sequential association of type II and type I receptors and the Smad protein cascades (3, 4). The binding of ligands to the receptors leads to the phosphorylation of Smad2 and Smad3 at their SSXS motif within the COOH termini. The phosphorylated Smad2 or Smad3 forms complexes with Smad4 and translocates into the nucleus, where they function as DNA-binding transcription factors. Recently, Smad3 was discovered to have the novel ability of regulating the proteasomal degradation of the nuclear proto-oncoproteins SnoN and Ski (5, 6) as well as the human enhancer of filmentation 1 (HEF1) (7).HEF1 is a member of a multiple domain docking protein Cas family including p130 cas and Efs that have been implicated as signaling mediators of diverse processes including cellular attachment, motility, growth factor responses, apoptosis, and oncogenic transformation (8). HEF1 was first isolated in a screen for human proteins with the ability to alter Saccharomyces cerevisiae morphology from round to filamentous hyperpolarized cells (9). Based upon its homology to p130 cas , another group independently isolated HEF1, named Cas-L (10). Members of this family share similar domains, with an aminoterminal Src homology 3 domain that binds polyproline-containing protein, a large central domain encompassing multiple tyrosine motifs that are recognized by the Src homology 2 domain protein upon phosphorylation, a serine-rich domain, and a carboxyl-terminal domain containing a helix-loop-helix motif (9, 11).Earlier studies have showed t...

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“…Many more intracellular and extracellular modular protein domains have been identi®ed (reviewed by Bork et al, 1997). However, their ligands are as yet unknown, and signi®cant portions of the newly described modules so far seem to be con®ned to a limited number of specialized proteins that this domain will also bind its proline-rich ligand in a way in which individual proline residues contact the domain directly as well as serve a sca olding function to maintain the polyproline II helical structure, as was documented for ligands to SH3, WW and pro®lin (Yu et al, 1994;Macias et al, 1996;Mahoney et al, 1997).…”

Section: Degeneracy In The`protein Recognition Code'mentioning

confidence: 99%

“…Although structurally distinct, the WW domain is functionally related to the SH3 domain; it also binds proline-rich ligands (Chen and Sudol, 1995;Macias et al, 1996). The name`WW' refers to one of the distinguishing features of the domain: the presence of two highly conserved tryptophan residues (W) which are spaced 20 ± 22 amino acids apart (Sudol, 1996a).…”

Section: Ww Rulesmentioning

confidence: 99%

“…The e determinant here allows for easy prediction between these two groups. For group I, the e determinant is an aliphatic amino acid in the second b strand of the domain, position bB6; whereas for the group II this position is occupied by an aromatic amino acid (Sudol, 1996a;Macias et al, 1996). It is important to note that in both groups the bB6 residue is preceded by two consecutive aromatic amino acids.…”

Section: Ww Rulesmentioning

confidence: 99%

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From Src Homology domains to other signaling modules: proposal of the `protein recognition code'

1998

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The study of oncogenes has illuminated many aspects of cellular signaling. The delineation and characterization of protein modules exempli®ed by Src Homology domains has revolutionized our understanding of the molecular events underlying signal transduction pathways. Several well characterized intracellular modules which mediate protein-protein interactions, namely SH2, SH3, PH, PTB, EH, PDZ, EVH1 and WW domains, are directly involved in the multitude of membrane, cytoplasmic and nuclear processes in multicellular and/or unicellular organisms. The modular character of these protein domains and their cognate motifs, the universality of their molecular function, their widespread occurrence, and the speci®city as well as the degeneracy of their interactions have prompted us to propose the concept of the`protein recognition code'. By a parallel analogy to the universal genetic code, we propose here that there will be a ®nite set of precise rules to govern and predict protein-protein interactions mediated by modules. Several rules of the`protein recognition code' have already emerged.

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Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide

Cited by 426 publications

References 22 publications

Common Mechanism of Ligand Recognition by Group II/III WW Domains

Common Mechanism of Ligand Recognition by Group II/III WW Domains

Atrophin-1-interacting Protein 4/Human Itch Is a Ubiquitin E3 Ligase for Human Enhancer of Filamentation 1 in Transforming Growth Factor-β Signaling Pathways

From Src Homology domains to other signaling modules: proposal of the `protein recognition code'

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