Dataset Information

CryoEM structure of the A.aeolicus WzmWzt transporter in the presence of the native O antigen and ATP

ABSTRACT:

SUBMITTER: Jochen Zimmer

PROVIDER: EMPIAR-11202 | biostudies-other |

REPOSITORIES: biostudies-other

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Publications

Molecular basis for polysaccharide recognition and modulated ATP hydrolysis by the O antigen ABC transporter.

Spellmon Nicholas N Muszyński Artur A Górniak Ireneusz I Vlach Jiri J Hahn David D Azadi Parastoo P Zimmer Jochen J

Nature communications 20220905 1

O antigens are ubiquitous protective extensions of lipopolysaccharides in the extracellular leaflet of the Gram-negative outer membrane. Following biosynthesis in the cytosol, the lipid-linked polysaccharide is transported to the periplasm by the WzmWzt ABC transporter. Often, O antigen secretion requires the chemical modification of its elongating terminus, which the transporter recognizes via a carbohydrate-binding domain (CBD). Here, using components from A. aeolicus, we identify the O antige ...[more]

PMID: 36064941

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Project description:Adenoviral (Ad) vectors show promise as platforms for vaccine applications against infectious diseases including HIV. However, the requirements for eliciting protective neutralizing antibody and cellular immune responses against HIV remain a major challenge. In a novel approach to generate 2F5- and 4E10-like antibodies, we engineered an Ad vector with the HIV membrane proximal ectodomain region (MPER) epitope displayed on the hypervariable region 2 (HVR2) of the viral hexon capsid, instead of expressed as a transgene. The structure and flexibility of MPER epitopes, and the structural context of these epitopes within viral vectors, play important roles in the induced host immune responses. In this regard, understanding the critical factors for epitope presentation would facilitate optimization strategies for developing viral vaccine vectors. Therefore we undertook a cryoEM structural study of this Ad vector, which was previously shown to elicit MPER-specific humoral immune responses. A subnanometer resolution cryoEM structure was analyzed with guided molecular dynamics simulations. Due to the arrangement of hexons within the Ad capsid, there are twelve unique environments for the inserted peptide that lead to a variety of conformations for MPER, including individual α-helices, interacting α-helices, and partially extended forms. This finding is consistent with the known conformational flexibility of MPER. The presence of an extended form, or an induced extended form, is supported by interaction of this vector with the human HIV monoclonal antibody 2F5, which recognizes 14 extended amino acids within MPER. These results demonstrate that the Ad capsid influences epitope structure, flexibility and accessibility, all of which affect the host immune response. In summary, this cryoEM structural study provided a means to visualize an epitope presented on an engineered viral vector and suggested modifications for the next generation of Ad vectors with capsid-incorporated HIV epitopes.

Dataset Information

CryoEM structure of the A.aeolicus WzmWzt transporter in the presence of the native O antigen and ATP

Publications

Molecular basis for polysaccharide recognition and modulated ATP hydrolysis by the O antigen ABC transporter.

Similar Datasets

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