Structural basis of the dynamic human CEACAM1 monomer-dimer equilibrium.
Structural basis of the dynamic human CEACAM1 monomer-dimer equilibrium.
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DOI:
10.1038/s42003-021-01871-2
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发表时间:
2021-03-19
影响因子:
5.9
通讯作者:
Blumberg RS
中科院分区:
文献类型:
--
作者:
Gandhi AK;Sun ZJ;Kim WM;Huang YH;Kondo Y;Bonsor DA;Sundberg EJ;Wagner G;Kuchroo VK;Petsko GA;Blumberg RS
Human (h) carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) function depends upon IgV-mediated homodimerization or heterodimerization with host ligands, including hCEACAM5, hTIM-3, PD-1, and a variety of microbial pathogens. However, there is little structural information available on how hCEACAM1 transitions between monomeric and dimeric states which in the latter case is critical for initiating hCEACAM1 activities. We therefore mutated residues within the hCEACAM1 IgV GFCC′ face including V39, I91, N97, and E99 and examined hCEACAM1 IgV monomer-homodimer exchange using differential scanning fluorimetry, multi-angle light scattering, X-ray crystallography and/or nuclear magnetic resonance. From these studies, we describe hCEACAM1 homodimeric, monomeric and transition states at atomic resolution and its conformational behavior in solution through NMR assignment of the wildtype (WT) hCEACAM1 IgV dimer and N97A mutant monomer. These studies reveal the flexibility of the GFCC’ face and its important role in governing the formation of hCEACAM1 dimers and selective heterodimers. To understand how hCEACAM1 transitions between monomeric and dimeric states that are required for its activity, Gandhi et al. investigate hCEACAM1 homodimeric, monomeric, and transition states and their behavior in solution. This study suggests the flexibility of the GFCC’ face and its role in governing the formation of hCEACAM1 dimers and selective heterodimers.
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影响因子:
4.6
作者:
Gandhi AK;Kim WM;Sun ZJ;Huang YH;Bonsor DA;Sundberg EJ;Kondo Y;Wagner G;Kuchroo VK;Petsko G;Blumberg RS
通讯作者:
Blumberg RS
影响因子:
16
作者:
Ergün, S;Kilic, N;Wagener, C
通讯作者:
Wagener, C
DOI:
10.1073/pnas.1509511112
发表时间:
2015-11-03
影响因子:
11.1
作者:
Bonsor, Daniel A.;Guenther, Sebastian;Sundberg, Eric J.
通讯作者:
Sundberg, Eric J.
影响因子:
2.7
作者:
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者:
BAX, A
影响因子:
6
作者:
Ebrahimnejad, A;Streichert, T;Brümmer, J
通讯作者:
Brümmer, J