PDBsum entry 2c0l

Transport protein/receptor

PDB id: 2c0l

Contents

Protein chains

292 a.a. *

122 a.a. *

Waters ×99

* Residue conservation analysis

PDB id:

2c0l

Name:

Transport protein/receptor

Title:

Tpr domain of human pex5p in complex with human mscp2

Structure:

Peroxisomal targeting signal 1 receptor. Chain: a. Fragment: tpr repeat domain, residues 298-602. Synonym: pex5p, peroxismore receptor 1, peroxin-5, peroxisomal c- terminal targeting signal import receptor, pts1-bp, pts1 receptor. Engineered: yes. Nonspecific lipid-transfer protein. Chain: b. Fragment: scp2 domain, residues 426-547.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å R-factor: 0.205 R-free: 0.256

Authors:

W.A.Stanley,P.Kursula,M.Wilmanns

Key ref:

W.A.Stanley et al. (2006). Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p. Mol Cell, 24, 653-663. PubMed id: 17157249 DOI: 10.1016/j.molcel.2006.10.024

Date:

05-Sep-05 Release date: 15-Nov-06

Protein chain

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

Seq: 639 a.a.

Struc: 292 a.a.*

Protein chain

P22307  (NLTP_HUMAN) -  Sterol carrier protein 2 from Homo sapiens

Seq: 547 a.a.

Struc: 122 a.a.

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

Enzyme reactions

• Enzyme class 2: Chain B: E.C.2.3.1.155 - acetyl-CoA C-myristoyltransferase.
• Reaction: tetradecanoyl-CoA + acetyl-CoA = 3-oxohexadecanoyl-CoA + CoA
• Enzyme class 3: Chain B: E.C.2.3.1.16 - acetyl-CoA C-acyltransferase.
• Reaction: an acyl-CoA + acetyl-CoA = a 3-oxoacyl-CoA + CoA
• Enzyme class 4: Chain B: E.C.2.3.1.176 - propanoyl-CoA C-acyltransferase.
• Reaction: choloyl-CoA + propanoyl-CoA = 3alpha,7alpha,12alpha-trihydroxy-24-oxo- 5beta-cholestan-26-oyl-CoA + CoA

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.molcel.2006.10.024

Mol Cell 24:653-663 (2006)

PubMed id: 17157249

Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p.

W.A.Stanley, F.V.Filipp, P.Kursula, N.Schüller, R.Erdmann, W.Schliebs, M.Sattler, M.Wilmanns.

ABSTRACT

Peroxisomes require the translocation of folded and functional target proteins of various sizes across the peroxisomal membrane. We have investigated the structure and function of the principal import receptor Pex5p, which recognizes targets bearing a C-terminal peroxisomal targeting signal type 1. Crystal structures of the receptor in the presence and absence of a peroxisomal target, sterol carrier protein 2, reveal major structural changes from an open, snail-like conformation into a closed, circular conformation. These changes are caused by a long loop C terminal to the 7-fold tetratricopeptide repeat segments. Mutations in residues of this loop lead to defects in peroxisomal import in human fibroblasts. The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function.

Selected figure(s)

Figure 3.
Figure 3. Structures of the Peroxisomal Import Receptor Pex5p(C) in the Presence and in the Absence of the Cargo mSCP2
Color coding for Pex5p(C) is as follows: TPR1-TPR3, cyan; TPR4, green; TPR5-TPR7, blue; 7C loop, connecting TPR7 and the C-terminal helical bundle, red; and C terminus, maroon. Color coding for mSCP2 is as follows: core domain, yellow; and C terminus including PTS1 motif, orange. The orientation of the receptor in (A) and (C) is identical. The ribbon of the Pex5p(C)/mSCP2 complex in (B) has been rotated by 60° around a horizontal axis within the paper plane with respect to the orientation in (A), to illustrate the mode of mSCP2 binding to the receptor. (D) Superimposed Pex5p(C) receptor structures in the presence and in the absence of mSCP2. The colors of the trace of the cargo-loaded conformation are as in (A)–(C), except that the conformational hinge regions are colored in orange. The trace of the apo-Pex5p(C) structure is in gray, except for the 7C loop, which is colored in faint red. The coordinates of TPR segments 1–4 were used for structural superposition using the program SSM (Krissinel and Henrick, 2004) (rmsd = 0.78 Å for 164 common residues). The largest structural deviations of up to 8 Å are observed at the 7C loop and adjacent regions and are indicated by a red arrow.

Figure 5.
Figure 5. Structural Determinants of mSCP2 Cargo Loading onto Pex5p(C)
(A) Stereo view of the 2F[O] − F[C] electron density, using phases from the refined model and contoured at 1σ, of the PTS1 motif from mSCP2 (gray) and some interacting residues from Pex5p and ordered solvent molecules (dark green).
(B) Pex5p(C)/mSCP2 complex formation by two distinct interfaces: C-terminal PTS1 motif from mSCP2 (orange)-central cavity of the circular TPR motif structure from Pex5p; secondary surface from mSCP2-C-terminal helical bundle from Pex5p. Ser600 is in a central position between the two surface patches, allowing the proper arrangement of the two cargo surface patches of Pex5p to support binding of mSCP2. The C terminus of the 7C loop (red) interacts by a few hydrogen bonds with the TPR1 segment.
(C) TPR4 motif of Pex5p(C), as observed in the cargo-loaded structure of the receptor. Specific interactions between TPR3 and TPR4, generating a circular conformation of Pex5p(C), are shown. Colors are as in Figure 3 and Figure 4, except that some of the bonds of residues from the C-terminal TPR motifs 5–7 and the 7C loop are colored in gray to allow illustrations of oxygen and nitrogen atoms. Hydrogen bonds are shown by dashed lines.

The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 24, 653-663) copyright 2006.

Figures were selected by an automated process.