Matches in SemOpenAlex for { <https://semopenalex.org/work/W4382199841> ?p ?o ?g. }
- W4382199841 endingPage "3145" @default.
- W4382199841 startingPage "3133" @default.
- W4382199841 abstract "The coordinated (dis)engagement of the membrane-bound T cell receptor (TCR)-CD3-CD4 complex from the peptide-major histocompatibility complex (pMHC) is fundamental to TCR signal transduction and T cell effector function. As such, an atomic-scale understanding would not only enhance our basic understanding of the adaptive immune response but would also accelerate the rational design of TCRs for immunotherapy. In this study, we explore the impact of the CD4 coreceptor on the TCR-pMHC (dis)engagement by constructing a molecular-level biomimetic model of the CD3-TCR-pMHC and CD4-CD3-TCR-pMHC complexes within a lipid bilayer. After allowing the system complexes to equilibrate (engage), we use steered molecular dynamics to dissociate (disengage) the pMHC. We find that 1) the CD4 confines the pMHC closer to the T cell by 1.8 nm at equilibrium; 2) CD4 confinement shifts the TCR along the MHC binding groove engaging a different set of amino acids and enhancing the TCR-pMHC bond lifetime; 3) the CD4 translocates under load increasing the interaction strength between the CD4-pMHC, CD4-TCR, and CD4-CD3; and 4) upon dissociation, the CD3-TCR complex undergoes structural oscillation and increased energetic fluctuation between the CD3-TCR and CD3-lipids. These atomic-level simulations provide mechanistic insight on how the CD4 coreceptor impacts TCR-pMHC (dis)engagement. More specifically, our results provide further support (enhanced bond lifetime) for a force-dependent kinetic proofreading model and identify an alternate set of amino acids in the TCR that dominate the TCR-pMHC interaction and could thus impact the design of TCRs for immunotherapy." @default.
- W4382199841 created "2023-06-28" @default.
- W4382199841 creator A5033666255 @default.
- W4382199841 creator A5041953526 @default.
- W4382199841 creator A5071498517 @default.
- W4382199841 date "2023-08-01" @default.
- W4382199841 modified "2023-10-14" @default.
- W4382199841 title "A dynamic biomimetic model of the membrane-bound CD4-CD3-TCR complex during pMHC disengagement" @default.
- W4382199841 cites W1031578623 @default.
- W4382199841 cites W1595347157 @default.
- W4382199841 cites W1607931568 @default.
- W4382199841 cites W1967359088 @default.
- W4382199841 cites W1968611188 @default.
- W4382199841 cites W1970932744 @default.
- W4382199841 cites W1974600311 @default.
- W4382199841 cites W1985349820 @default.
- W4382199841 cites W1987327282 @default.
- W4382199841 cites W1988091837 @default.
- W4382199841 cites W1990771438 @default.
- W4382199841 cites W1993369787 @default.
- W4382199841 cites W1998000103 @default.
- W4382199841 cites W1999613945 @default.
- W4382199841 cites W2001676859 @default.
- W4382199841 cites W2002780937 @default.
- W4382199841 cites W2011584482 @default.
- W4382199841 cites W2015214828 @default.
- W4382199841 cites W2021520922 @default.
- W4382199841 cites W2024134244 @default.
- W4382199841 cites W2032361037 @default.
- W4382199841 cites W2042527516 @default.
- W4382199841 cites W2050615016 @default.
- W4382199841 cites W2072659663 @default.
- W4382199841 cites W2074529126 @default.
- W4382199841 cites W2081693079 @default.
- W4382199841 cites W2103945336 @default.
- W4382199841 cites W2121727772 @default.
- W4382199841 cites W2124555673 @default.
- W4382199841 cites W2125337252 @default.
- W4382199841 cites W2126459563 @default.
- W4382199841 cites W2127908488 @default.
- W4382199841 cites W2128572087 @default.
- W4382199841 cites W2132262459 @default.
- W4382199841 cites W2132827455 @default.
- W4382199841 cites W2134762386 @default.
- W4382199841 cites W2141026552 @default.
- W4382199841 cites W2144460514 @default.
- W4382199841 cites W2152148059 @default.
- W4382199841 cites W2152645204 @default.
- W4382199841 cites W2160287573 @default.
- W4382199841 cites W2168269595 @default.
- W4382199841 cites W2170711116 @default.
- W4382199841 cites W2171006798 @default.
- W4382199841 cites W2171268876 @default.
- W4382199841 cites W2195140122 @default.
- W4382199841 cites W2206954826 @default.
- W4382199841 cites W2277057157 @default.
- W4382199841 cites W2323919183 @default.
- W4382199841 cites W2345307871 @default.
- W4382199841 cites W2347077379 @default.
- W4382199841 cites W2405075761 @default.
- W4382199841 cites W2411913461 @default.
- W4382199841 cites W2417253274 @default.
- W4382199841 cites W2507723354 @default.
- W4382199841 cites W2510475640 @default.
- W4382199841 cites W2566732684 @default.
- W4382199841 cites W2579751480 @default.
- W4382199841 cites W2606511608 @default.
- W4382199841 cites W2623055862 @default.
- W4382199841 cites W2762980752 @default.
- W4382199841 cites W2778188986 @default.
- W4382199841 cites W2783439615 @default.
- W4382199841 cites W2800263460 @default.
- W4382199841 cites W2803300773 @default.
- W4382199841 cites W2884809460 @default.
- W4382199841 cites W2896812555 @default.
- W4382199841 cites W2898119186 @default.
- W4382199841 cites W2901906577 @default.
- W4382199841 cites W2905232362 @default.
- W4382199841 cites W2911501853 @default.
- W4382199841 cites W2933229048 @default.
- W4382199841 cites W2947608680 @default.
- W4382199841 cites W2950669909 @default.
- W4382199841 cites W2952711759 @default.
- W4382199841 cites W2957203663 @default.
- W4382199841 cites W2958230540 @default.
- W4382199841 cites W2965645347 @default.
- W4382199841 cites W2971032307 @default.
- W4382199841 cites W2981233274 @default.
- W4382199841 cites W3006615134 @default.
- W4382199841 cites W3009031092 @default.
- W4382199841 cites W3087102249 @default.
- W4382199841 cites W3099878876 @default.
- W4382199841 cites W3103145119 @default.
- W4382199841 cites W3110685564 @default.
- W4382199841 cites W3111523834 @default.
- W4382199841 cites W3131314974 @default.
- W4382199841 cites W3157824041 @default.
- W4382199841 cites W3175918178 @default.