ABCMdb

ABCD3 p.Leu207Pro

Predicted by SNAP2:	A: N (53%), C: N (61%), D: D (75%), E: D (75%), F: N (61%), G: D (75%), H: D (71%), I: N (97%), K: D (80%), M: N (93%), N: D (63%), P: D (80%), Q: D (66%), R: D (75%), S: D (66%), T: N (78%), V: N (97%), W: D (59%), Y: D (66%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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Publications
[hide] Function of the PEX19-binding site of human adreno... J Biol Chem. 2005 Jun 3;280(22):21176-82. Epub 2005 Mar 21. Halbach A, Lorenzen S, Landgraf C, Volkmer-Engert R, Erdmann R, Rottensteiner H
Function of the PEX19-binding site of human adrenoleukodystrophy protein as targeting motif in man and yeast. PMP targeting is evolutionarily conserved.
J Biol Chem. 2005 Jun 3;280(22):21176-82. Epub 2005 Mar 21., [PMID:15781447]

Abstract [show]
We predicted in human peroxisomal membrane proteins (PMPs) the binding sites for PEX19, a key player in the topogenesis of PMPs, by virtue of an algorithm developed for yeast PMPs. The best scoring PEX19-binding site was found in the adrenoleukodystrophy protein (ALDP). The identified site was indeed bound by human PEX19 and was also recognized by the orthologous yeast PEX19 protein. Likewise, both human and yeast PEX19 bound with comparable affinities to the PEX19-binding site of the yeast PMP Pex13p. Interestingly, the identified PEX19-binding site of ALDP coincided with its previously determined targeting motif. We corroborated the requirement of the ALDP PEX19-binding site for peroxisomal targeting in human fibroblasts and showed that the minimal ALDP fragment targets correctly also in yeast, again in a PEX19-binding site-dependent manner. Furthermore, the human PEX19-binding site of ALDP proved interchangeable with that of yeast Pex13p in an in vivo targeting assay. Finally, we showed in vitro that most of the predicted binding sequences of human PMPs represent true binding sites for human PEX19, indicating that human PMPs harbor common PEX19-binding sites that do resemble those of yeast. Our data clearly revealed a role for PEX19-binding sites as PMP-targeting motifs across species, thereby demonstrating the evolutionary conservation of PMP signal sequences from yeast to man.

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No. Sentence Comment
70 Systematic truncations of the ALDP-(67-84) peptide, aimed to deter- TABLE I Plasmids used Plasmid Description Primer pair Source or Ref. pEGFP-C1 Clontech pUG35 34 pPC97 35 pPC86 35 pHPR131 ADH2pr-PTS2-DsRed 36 pKat61 ScPEX19 in pPC86 15 pKat79 ScPEX19 in pGex4T-2 15 pKat145 ScPEX13 (173-258) in pPC97 15 pHPR262 ScPEX13 (173-258) L207P in pPC97 15 pMS21 ScPEX13 (221-310) in pUG35 15 pHPR241 ScPEX13 (200-310) in pUG35 15 pAH5 HsPEX19 in pGEX4T-1 BamHI-SalI RE734/735 This study pAH7 HsPEX19 (2-299) in pPC86 SalI-BglII RE976/977 This study pAH8 ALDP (69-83) in pPC97 XbaI-BamHI RE1034/1035 This study pAH9 ALDP (66-87) in pUG35 XbaI-BamHI RE1065/1066 This study pAH10 ALDP (66-164) in pUG35 XbaI-BamHI RE1065/1067 This study pAH11 ALDP (66-87) in pMS21 XbaI-BamHI RE1065/1068 This study pAH23 ALDP (87-164) in pUG35 XbaI-BamHI RE1166/1067 This study pAH27 ALDP (87-164) in pEGFP-C1 EcoRI-SalI RE1198/1199 This study pAH28 ALDP (66-87) in pEGFP-C1 EcoRI-SalI RE1200/1201 This study pAH29 ALDP (66-164) in pEGFP-C1 EcoRI-SalI RE1200/1199 This study mine a core binding site, were synthesized and again tested for PEX19 binding. Login to comment
91 Moreover, the L207P point mutation, which specifically abolishes the ScPex13p-(173-258) interaction with ScPex19p (15), also caused a loss of HsPEX19 binding (Fig. 2C). Login to comment
117 The same fragment but with a Leu to Pro mutation at position 207 was also tested. Login to comment