An investigation of the YidC-mediated membrane insertion of Pf3 coat protein using molecular dynamics simulations

Polasa, Adithya; Hettige, Jeevapani J.; Immadisetty, Kalyan; Moradi, Mahmoud

doi:10.1016/j.bpj.2021.11.1126

Cited by 1 publication

(12 citation statements)

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“…The results of this study support the theory that the C2 loop plays a significant part in the conformational dynamics of YidC. Previous studies have revealed that the YidC transmembrane (TM) region is crucial for the membrane protein insertion mechanism 20,79,80 . In order to examine the impact of deleting the PD and C2 loop on the TM helices, the helical angle between each pair of TMs was measured in this work (Fig.…”

Section: Resultssupporting

confidence: 88%

“…We are interested in the significance of the cytoplasmic C2 loop and extracellular periplasmic domain (PD). Previous studies have highlighted the critical role of the C2 loop in determining YidC's conformation and function in gram-positive bacteria 20,72 . We are interested in learning more about the functions of the PD (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…To analyze the water inside the groove region, we counted the number of water molecules within 5 Å of R366. Principle component analysis (PCA) was performed for each trajectory using PRODY 20,64,76 , taking only protein C α atoms into account.…”

Section: Methodsmentioning

confidence: 99%

“…It also plays a vital role in the insertion and positioning of membrane proteins in bacteria [17][18][19] . Insertase proteins, such as YidC, have been exhaustively investigated to determine their importance for the insertion of proteins into membranes 20 , and many researchers have found evidence of YidC in conjunction with the Sec-complex [2][3][4][5][6][7][8] , which act to insert peptides into the membrane bilayer through the Signal Recognition Particle (SRP) mechanism. In addition, YidC may fold and insert polypeptides independent of the Sec-dependent pathway, 3,[21][22][23][24][25][26][27][28] and it is essential for the insertion of small phage coat proteins like Pf3 coat and M13 in a Sec-independent pathway.…”

Section: Introductionmentioning

confidence: 99%

“…The hydrophilic groove inside the membrane core of YidC increases the rate of accepting the hydrophilic moieties of a substrate into the membrane [49][50][51][52] . During its independent insertion mechanism, gram-positive YidC also goes through several conformational changes, including widening of the TM region and hydration and dehydration of the hydrophilic groove 20 . Additionally, a broad range of interactions with the incoming protein is involved at each step of the insertion process.…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the Inter-domain Decoupling in the Gram-negative Bacterial Membrane Insertase

Polasa

Moradi

2022

Preprint

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YidC is a protein found in membranes that plays an important role in the process of inserting newly generated proteins into lipid membranes. The SecYEG-dependent complex is responsible for inserting proteins into the lipid bilayer, and this process is facilitated by YidC. In addition, YidC acts as a chaperone during the folding processes of proteins. Multiple investigations have conclusively shown that the gram-positive bacterium YidC has SecY-independent insertion mechanisms. Through the use of microsecond level all-atom molecular dynamics simulations, we have carried out the first in-depth investigation of the YidC protein originating from gram-negative bacteria. This research sheds light on the significance of several structural areas related to YidC at an atomic level by utilizing equilibrium molecular dynamics (MD) simulations. In this research, multiple models of YidC inside the lipid bilayer were constructed in order to achieve a deeper understanding of the critical role of the C2 loop and the extra periplasmic domain present in gram-negative YidC. According to the results of our research, the C2 loop is responsible for the overall stabilization of the protein, most notably in the transmembrane region, and it also has an allosteric influence on the periplasmic domain. We have found critical interactions that contribute to the stability of the protein as well as its functional aspect. Finally, our study provides a hypothetical SecY-independent insertion mechanism for gram-negative bacterial YidC.

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Section: Resultssupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%