6x8u
From Proteopedia
Crystal structure of 3D11 Fab in complex with Plasmodium berghei circumsporozoite protein Mixed peptide
Structural highlights
FunctionCSP_PLABA Essential sporozoite protein (PubMed:15630135, PubMed:16207248, PubMed:18005753, PubMed:21262960, PubMed:6985745). In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands (PubMed:16207248, PubMed:21262960). In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes (PubMed:15630135, PubMed:18005753, PubMed:21262960, PubMed:6985745). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (PubMed:18005753).[1] [2] [3] [4] [5] In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.[6] [7] Publication Abstract from PubMedPlasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against P. falciparum (Pf) - has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to P. berghei CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites. Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11.,Kucharska I, Thai E, Srivastava A, Rubinstein JL, Pomes R, Julien JP Elife. 2020 Nov 30;9:e59018. doi: 10.7554/eLife.59018. PMID:33253113[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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