PDBsum entry 4o2x

Transport protein

PDB id: 4o2x

Contents

Protein chains

457 a.a.

PDB id:

4o2x

Name:

Transport protein

Title:

Structure of a malarial protein

Structure:

Maltose-binding periplasmic protein, atp-dependent clp protease adaptor protein clps containing protein chimeric construct. Chain: a, b. Fragment: mbp residues, malarial clps residues 73-192. Synonym: mbp, mmbp. Engineered: yes. Mutation: yes

Source:

Escherichia coli, plasmodium falciparum (isolate 3d7). Organism_taxid: 83333, 36329. Strain: k12. Gene: male, b4034, jw3994, mal13p1.111. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.70Å R-factor: 0.189 R-free: 0.239

Authors:

A.P.Ahyoung,A.Koehl,D.Cascio,P.F.Egea

Key ref:

A.P.AhYoung et al. (2016). Structure of a putative ClpS N-end rule adaptor protein from the malaria pathogen Plasmodium falciparum. Protein Sci, 25, 689-701. PubMed id: 26701219 DOI: 10.1002/pro.2868

Date:

17-Dec-13 Release date: 24-Dec-14

Protein chains

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 457 a.a.*

Protein chains

Q8IEB2  (Q8IEB2_PLAF7) -  ATP-dependent Clp protease adapter protein ClpS from Plasmodium falciparum (isolate 3D7)

Seq: 192 a.a.

Struc: 457 a.a.*

* PDB and UniProt seqs differ at 73 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.?
• Enzyme class 2: E.C.3.4.21.92 - endopeptidase Clp.
• Reaction: Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are cleaved (such as succinyl-Leu-Tyr-|-NHMEC; and Leu-Tyr-Leu-|-Tyr-Trp, in which the cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp- bond also occurs).

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.

DOI no: 10.1002/pro.2868

Protein Sci 25:689-701 (2016)

PubMed id: 26701219

Structure of a putative ClpS N-end rule adaptor protein from the malaria pathogen Plasmodium falciparum.

A.P.AhYoung, A.Koehl, C.L.Vizcarra, D.Cascio, P.F.Egea.

ABSTRACT

The N-end rule pathway uses an evolutionarily conserved mechanism in bacteria and eukaryotes that marks proteins for degradation by ATP-dependent chaperones and proteases such as the Clp chaperones and proteases. Specific N-terminal amino acids (N-degrons) are sufficient to target substrates for degradation. In bacteria, the ClpS adaptor binds and delivers N-end rule substrates for their degradation upon association with the ClpA/P chaperone/protease. Here, we report the first crystal structure, solved at 2.7 Å resolution, of a eukaryotic homolog of bacterial ClpS from the malaria apicomplexan parasite Plasmodium falciparum (Pfal). Despite limited sequence identity, Plasmodium ClpS is very similar to bacterial ClpS. Akin to its bacterial orthologs, plasmodial ClpS harbors a preformed hydrophobic pocket whose geometry and chemical properties are compatible with the binding of N-degrons. However, while the N-degron binding pocket in bacterial ClpS structures is open and accessible, the corresponding pocket in Plasmodium ClpS is occluded by a conserved surface loop that acts as a latch. Despite the closed conformation observed in the crystal, we show that, in solution, Pfal-ClpS binds and discriminates peptides mimicking bona fide N-end rule substrates. The presence of an apicoplast targeting peptide suggests that Pfal-ClpS localizes to this plastid-like organelle characteristic of all Apicomplexa and hosting most of its Clp machinery. By analogy with the related ClpS1 from plant chloroplasts and cyanobacteria, Plasmodium ClpS likely functions in association with ClpC in the apicoplast. Our findings open new venues for the design of novel anti-malarial drugs aimed at disrupting parasite-specific protein quality control pathways.