Kinetoplastid membrane protein‐11 adopts a four‐helix bundle fold in <scp>DPC</scp> micelle

Lim, Lynette; Ee, Shermaine; Fu, Jing; Tan, Yanming; He, Cynthia Y.; Song, Jianxing

doi:10.1002/1873-3468.12891

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…Only one protein, the kinetoplastid membrane protein-11 (KMP11), had a positive hit that covered >80% of the queried sequence length. This was a KMP11 ortholog from the closely related Trypanosoma brucei brucei (PDB accession 5Y70) (48). Taking it as reference, we modeled the T. cruzi KMP11 onto it using MODELER (49).…”

Section: Methodsmentioning

confidence: 99%

In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

et al. 2019

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Trypanosoma cruzi infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of the disease, this is usually asymptomatic and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when life-threatening heart and/or gut tissue disruptions occur in ~30% of those chronically infected. By then, the drugs' efficacy is reduced, but not their associated high toxicity. Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection and/or the development of symptoms would be a breakthrough in the management of the disease. Current vaccine candidates are mostly based on the delivery of single antigens or a few different antigens. Nevertheless, due to the high biological complexity of the parasite, targeting as many antigens as possible would be desirable. In this regard, an epitope-based vaccine design could be a well-suited approach. With this aim, we have gone through publicly available databases to identify T. cruzi epitopes from several antigens. By means of a computer-aided strategy, we have prioritized a set of epitopes based on sequence conservation criteria, projected population coverage of Latin American population, and biological features of their antigens of origin. Fruit of this analysis, we provide a selection of CD8+ T cell, CD4+ T cell, and B cell epitopes that have <70% identity to human or human microbiome protein sequences and represent the basis toward the development of an epitope-based vaccine against T. cruzi.

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Section: Methodsmentioning

confidence: 99%

In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

et al. 2019

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“…The localization of ETP5 suggests that in A. deanei there is a host-derived structure that connects the three DNA-containing compartments (nucleus, mitochondrion, and endosymbiont) with the basal body. ETP5 likely interacts with these three compartments by direct interaction with the lipids present in their outer membranes 57 . Importantly, in trypanosomes, division of the basal body marks the transition from the G phase to the S phase in the cell cycle 58 .…”

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confidence: 99%

Evolution of a putative, host-derived endosymbiont division ring and symbiosis-induced proteome rearrangements in the trypanosomatid Angomonas deanei

Morales

Ehret

Poschmann

et al. 2021

Preprint

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The transformation of endosymbiotic bacteria into genetically integrated organelles was central to eukaryote evolution. During organellogenesis, control over endosymbiont division, proteome composition, and physiology largely shifted from the endosymbiont to the host cell nucleus. However, to understand the order and timing of events underpinning organellogenesis novel model systems are required. The trypanosomatid Angomonas deanei contains β-proteobacterial endosymbiont that divides synchronously with the host, contributes essential metabolites to host cell metabolism, and transferred one bacterial gene [encoding an ornithine cyclodeaminase (OCD)] to the nucleus. However, the molecular mechanisms mediating the intricate host/symbiont interactions are largely unexplored. Here we identified seven nucleus-encoded proteins by protein mass spectrometry that are targeted to the endosymbiont. Expression of fluorescent fusion proteins revealed recruitment of these proteins to specific sites within the endosymbiont including its cytoplasm and a ring-shaped structure surrounding its division site. This structure remarkably resembles in shape and predicted functions mitochondrial and plastid division machineries. The endosymbiotic gene transfer-derived OCD localizes to glycosomes instead of being retargeted to the endosymbiont. Hence, scrutiny of protein re-localization patterns that are induced by endosymbiosis, yielded profound insights into how an endosymbiotic relationship can stabilize and deepen over time far beyond the level of metabolite exchange.

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Host-symbiont interactions in Angomonas deanei include the evolution of a host-derived dynamin ring around the endosymbiont division site

et al. 2023

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Kinetoplastid membrane protein‐11 adopts a four‐helix bundle fold in DPC micelle

Abstract: The structure coordinate of KMP11 in DPC micelle has been deposited in PDB with ID of 5Y70 and the associated NMR data were deposited in BMRB with ID of 36112.

Cited by 4 publications

References 45 publications

In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

Evolution of a putative, host-derived endosymbiont division ring and symbiosis-induced proteome rearrangements in the trypanosomatid Angomonas deanei

Host-symbiont interactions in Angomonas deanei include the evolution of a host-derived dynamin ring around the endosymbiont division site

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