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dc.contributor.authorGandhi, A.K.
dc.contributor.authorSun, Z.-Y.J.
dc.contributor.authorKim, W.M.
dc.contributor.authorHuang, Y.-H.
dc.contributor.authorKondo, Y.
dc.contributor.authorBonsor, D.A.
dc.contributor.authorSundberg, E.J.
dc.contributor.authorWagner, G.
dc.contributor.authorKuchroo, V.K.
dc.contributor.authorPetsko, G.A.
dc.contributor.authorBlumberg, R.S.
dc.date.accessioned2021-04-12T16:16:39Z
dc.date.available2021-04-12T16:16:39Z
dc.date.issued2021-03-19
dc.identifier.urihttp://hdl.handle.net/10713/15163
dc.description.abstractHuman (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. Copyright 2021, The Author(s).en_US
dc.description.sponsorshipThis work was supported by the NIH Grant 5R01DK051362-21 and the High Pointe Foundation to R.S.B., and 5P01AI073748-09 to V.K.K.en_US
dc.description.urihttps://doi.org/10.1038/s42003-021-01871-2en_US
dc.language.isoen_USen_US
dc.publisherNature Researchen_US
dc.relation.ispartofCommunications Biology
dc.subjectmonomer-dimer equilibriumen_US
dc.subject.meshCarcinoembryonic Antigen--physiologyen_US
dc.titleStructural basis of the dynamic human CEACAM1 monomer-dimer equilibriumen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s42003-021-01871-2
dc.identifier.pmid33742094


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