A Proposal for a Consolidated Structural Model of the CagY Protein of Helicobacter pylori.
Int J Mol Sci
; 24(23)2023 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-38069104
ABSTRACT
CagY is the largest and most complex protein from Helicobacter pylori's (Hp) type IV secretion system (T4SS), playing a critical role in the modulation of gastric inflammation and risk for gastric cancer. CagY spans from the inner to the outer membrane, forming a channel through which Hp molecules are injected into human gastric cells. Yet, a tridimensional structure has been reported for only short segments of the protein. This intricate protein was modeled using different approaches, including homology modeling, ab initio, and deep learning techniques. The challengingly long middle repeat region (MRR) was modeled using deep learning and optimized using equilibrium molecular dynamics. The previously modeled segments were assembled into a 1595 aa chain and a 14-chain CagY multimer structure was assembled by structural alignment. The final structure correlated with published structures and allowed to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric cells. The model confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain may function as a contractile region playing an essential role in the modulating activity of CagY on tissue inflammation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Helicobacter pylori
/
Infecções por Helicobacter
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Gastrite
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article