PDBsum entry 1fch

Signaling protein

PDB id: 1fch

Contents

Protein chain

302 a.a. *

Ligands

TYR-GLN-SER-LYS-LEU ×2

Waters ×241

* Residue conservation analysis

PDB id:

1fch

Name:

Signaling protein

Title:

Crystal structure of the pts1 complexed to the tpr region of human pex5

Structure:

Peroxisomal targeting signal 1 receptor. Chain: a, b. Fragment: c-terminal tpr region. Synonym: peroxismore receptor 1, pts1-bp, peroxin-5, pts1 receptor. Engineered: yes. Pts1-containing peptide. Chain: c, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized

Biol. unit:

Octamer (from PQS)

Resolution:

2.20Å R-factor: 0.194 R-free: 0.224

Authors:

G.J.Gatto Jr.,B.V.Geisbrecht,S.J.Gould,J.M.Berg

Key ref:

G.J.Gatto et al. (2000). Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. Nat Struct Biol, 7, 1091-1095. PubMed id: 11101887 DOI: 10.1038/81930

Date:

18-Jul-00 Release date: 06-Dec-00

Protein chains

P50542  (PEX5_HUMAN) -  Peroxisomal targeting signal 1 receptor from Homo sapiens

Seq: 639 a.a.

Struc: 302 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/81930

Nat Struct Biol 7:1091-1095 (2000)

PubMed id: 11101887

Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5.

G.J.Gatto, B.V.Geisbrecht, S.J.Gould, J.M.Berg.

ABSTRACT

Many proteins contain targeting signals within their sequences that specify their delivery to particular organelles. The peroxisomal targeting signal-1 (PTS1) is a C-terminal tripeptide that is sufficient to direct proteins into peroxisomes. The PTS1 sequence closely approximates Ser-Lys-Leu-COO-. PEX5, the receptor for PTS1, interacts with the signal via a series of tetratricopeptide repeats (TPRs) within its C-terminal half. Here we report the crystal structure of a fragment of human PEX5 that includes all seven predicted TPR motifs in complex with a pentapeptide containing a PTS1 sequence. Two clusters of three TPRs almost completely surround the peptide, while a hinge region, previously identified as TPR4, forms a distinct structure that enables the two sets of TPRs to form a single binding site. This structure reveals the molecular basis for PTS1 recognition and demonstrates a novel mode of TPR-peptide interaction.

Selected figure(s)

Figure 2.
Figure 2. Schematic views of the PEX5 -PTS1 complex. a, A view down the long axis of the peptide (ball-and-stick, in red). TPRs 1 -3 are shown in yellow, TPRs 5 -7 in cyan, the hinge region ('TPR4') in green, and other regions in white. b, A view rotated 90° from (a). c, Stereo view of the C trace of the complex, in the same orientation as (a). Peptide is in red. d, Schematic representation of crystal packing if peptide binding occurs by TPR clusters from the same receptor molecule. TPRs 1 -3 are represented by the oval; TPRs 5 -7 by the rectangle. The white bar represents the peptide binding site. e, Similar diagram as in (d), showing crystal packing if peptide recognition occurs by TPR clusters from neighboring molecules. Dashed lines in (a,b) and (d,e) indicate the potential path of the protein chain for which no electron density was observed. Molecular representations in (a -c), as well as Fig. 4a,b, were generated using MOLSCRIPT33.

Figure 4.
Figure 4. Relationship of peptide with the TPR clusters. a, View of the interaction of TPRs 1 -3 (yellow) with the peptide ligand (ball-and-stick, in red). b, View of the interaction of TPRs 5 -7 (cyan) with the peptide ligand. c, Molecular surface representation of TPRs 1 -3 interacting with the peptide ligand (yellow). Blue represents regions of positive potential and red represents regions of negative potential, at the 10 kT e^-1 level. d, Similar representation as in (c), showing TPRs 5 -7 with peptide. (c,d) were generated using GRASP35.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 1091-1095) copyright 2000.

Figures were selected by an automated process.