The ScPex13p SH3 Domain Exposes Two Distinct Binding Sites for Pex5p and Pex14p

Pires, Juliana Rico; Hong, Xinji; Brockmann, Christoph; Volkmer, Rudolf; Schneider‐Mergener, Jens; Oschkinat, Hartmut; Erdmann, Ralf

doi:10.1016/s0022-2836(03)00039-1

Cited by 76 publications

(54 citation statements)

References 45 publications

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“…However, studies with Pex13p show that it can bind both conventional PXXP-containing peptides in the usual way, as well as a second, non-PXXP peptide, that binds at a novel, noncanonical pocket on the same SH3. Both peptides can bind to the Pex13p SH3 simultaneously (Pires et al, 2003). Therefore, it would not be unprecedented to find an SH3 whose overall structure is similar to that of most other SH3s, but whose binding surface is very different, as we have presented evidence here concerning the SH3-C of Crk II.…”

Section: Resultsmentioning

confidence: 69%

Transactivation of Abl by the Crk II adapter protein requires a PNAY sequence in the Crk C-terminal SH3 domain

et al. 2005

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To gain a better understanding of how Crk II regulates the function of the Abl tyrosine kinase, we explored the function of the C-terminal linker and SH3 domain, a region of Crk II that is still poorly understood. Molecular modeling, tryptophan fluorescence, and covariation sequence alignment indicate that the Crk-SH3-C has a unique binding groove and RT loop not observed in typical SH3 domains. Based on these models, we made a series of mutations in the linker and in residues predicted to destabilize the putative binding pocket and RT loop. In Abl transactivation assays, Y222F and P225A mutations in the linker resulted in strong transactivation of Abl by Crk II. However, mutations predicted to be at the surface of the Crk SH3-C were not activators of Abl. Interestingly, combinations of activating mutations of Crk II with mutations in the highly conserved PNAY sequence in the SH3-C inactivated the activating mutations, suggesting that the SH3-C is necessary for activation. Our data provide insight into the role of highly conserved residues in the Crk-SH3-C, suggesting a mechanism for how the linker and the Crk-SH3-C function in the transactivation of the Abl tyrosine kinase.

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Section: Resultsmentioning

confidence: 69%

Transactivation of Abl by the Crk II adapter protein requires a PNAY sequence in the Crk C-terminal SH3 domain

et al. 2005

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“…Prominent examples are two typical WXXX(F/Y) motifs of S. cerevisiae Pex5 (18,21) or one of the three WXXX(F/Y) motifs of Trypanosoma brucei Pex5 (22). These sequences may mediate the interaction with other peroxins, as shown for human and yeast Pex5 motifs, which both can interact with the Src homology 3 domain of Pex13 (8,13,24,25).…”

Section: In Human Cells This Interaction Is Mediated By Seven Consermentioning

confidence: 98%

A Novel Pex14 Protein-interacting Site of Human Pex5 Is Critical for Matrix Protein Import into Peroxisomes

Neuhaus

Kooshapur

Wolf

et al. 2014

Journal of Biological Chemistry

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“…A. thaliana PEX7 also bind the N-terminus of PEX13 in a yeast two-hybrid assay (Mano et al, 2006). PEX13 binds PEX14 in mammals via an interaction between the SH3 domain of PEX13 and the PXXP motif of PEX14 (Pires et al, 2003). In mammals, PEX13 interacts with PEX5, PEX14 and PEX19 through a conserved N-terminal region comprising residues 21-70 (Azevedo and Schliebs, 2006;Itoh and Fujiki, 2006).…”

Section: Docking Complexmentioning

confidence: 99%

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

Lanyon‐Hogg

Warriner

Baker

2010

Biology of the Cell

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Peroxisomes are a family of organelles which have many unusual features. They can arise de novo from the endoplasmic reticulum by a still poorly characterized process, yet possess a unique machinery for the import of their matrix proteins. As peroxisomes lack DNA, their function, which is highly variable and dependent on developmental and/or environmental conditions, is determined by the post-translational import of specific metabolic enzymes in folded or oligomeric states. The two classes of matrix targeting signals for peroxisomal proteins [PTS1 (peroxisomal targeting signal 1) and PTS2] are recognized by cytosolic receptors [PEX5 (peroxin 5) and PEX7 respectively] which escort their cargo proteins to, or possibly across, the peroxisome membrane. Although the membrane translocation mechanism remains unclear, it appears to be driven by thermodynamically favourable binding interactions. Recycling of the receptors from the peroxisome membrane requires ATP hydrolysis for two linked processes: ubiquitination of PEX5 (and the PEX7 co-receptors in yeast) and the function of two peroxisome-associated AAA (ATPase associated with various cellular activities) ATPases, which play a role in recycling or turnover of the ubiquitinated receptors. This review summarizes and integrates recent findings on peroxisome matrix protein import from yeast, plant and mammalian model systems, and discusses some of the gaps in our understanding of this remarkable protein transport system.

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The ScPex13p SH3 Domain Exposes Two Distinct Binding Sites for Pex5p and Pex14p

Cited by 76 publications

References 45 publications

Transactivation of Abl by the Crk II adapter protein requires a PNAY sequence in the Crk C-terminal SH3 domain

Transactivation of Abl by the Crk II adapter protein requires a PNAY sequence in the Crk C-terminal SH3 domain

A Novel Pex14 Protein-interacting Site of Human Pex5 Is Critical for Matrix Protein Import into Peroxisomes

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

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