4O2X

Structure of a malarial protein

4O2X の概要

• エントリーDOI: 10.2210/pdb4o2x/pdb
• 分子名称: Maltose-binding periplasmic protein, ATP-dependent Clp protease adaptor protein ClpS containing protein chimeric construct (1 entity in total)
• 機能のキーワード: clps, proteolysis, clp atpase protease, apicoplast, transport protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112990.07

構造登録者

AhYoung, A.P.,Koehl, A.,Cascio, D.,Egea, P.F. (登録日: 2013-12-17, 公開日: 2014-12-24, 最終更新日: 2023-09-20)

主引用文献

AhYoung, A.P.,Koehl, A.,Vizcarra, C.L.,Cascio, D.,Egea, P.F.
Structure of a putative ClpS N-end rule adaptor protein from the malaria pathogen Plasmodium falciparum.
Protein Sci., 25:689-701, 2016

PubMed 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.

PubMed: 26701219
DOI: 10.1002/pro.2868

実験手法

X-RAY DIFFRACTION (2.7 Å)