We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

7ua2

From Proteopedia

Jump to: navigation, search

Pfs230 D1 domain in complex with 230AL-18

Structural highlights

7ua2 is a 3 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.19Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P230_PLAF7 Gametocyte surface protein required for male/female gamete fusion. Also required for male gamete exflagellation and interaction with erythrocytes.^[1]

Publication Abstract from PubMed

Pfs230 domain 1 (Pfs230D1) is an advanced malaria transmission-blocking vaccine antigen demonstrating high functional activity in clinical trials. However, the structural and functional correlates of transmission-blocking activity are not defined. Here, we characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccinees immunized with Pfs230D1. These hmAbs exhibited diverse transmission-reducing activity, yet all bound to Pfs230D1 with nanomolar affinity. We compiled epitope-binning data for seventeen hmAbs and structures of nine hmAbs complexes to construct a high-resolution epitope map and revealed that potent transmission-reducing hmAbs bound to one face of Pfs230D1, while non-potent hmAbs bound to the opposing side. The structure of Pfs230D1D2 revealed that non-potent transmission-reducing epitopes were occluded by the second domain. The hmAb epitope map delineated binary hmAb combinations that synergized for extremely high-potency, transmission-reducing activity. This work provides a high-resolution guide for structure-based design of enhanced immunogens and informs diagnostics that measure the transmission-reducing response.

A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine.,Tang WK, Coelho CH, Miura K, Nguemwo Tentokam BC, Salinas ND, Narum DL, Healy SA, Sagara I, Long CA, Duffy PE, Tolia NH Immunity. 2023 Feb 14;56(2):433-443.e5. doi: 10.1016/j.immuni.2023.01.012. PMID:36792576^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Eksi S, Czesny B, van Gemert GJ, Sauerwein RW, Eling W, Williamson KC. Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production. Mol Microbiol. 2006 Aug;61(4):991-8. doi: 10.1111/j.1365-2958.2006.05284.x. PMID:16879650 doi:http://dx.doi.org/10.1111/j.1365-2958.2006.05284.x
↑ Tang WK, Coelho CH, Miura K, Nguemwo Tentokam BC, Salinas ND, Narum DL, Healy SA, Sagara I, Long CA, Duffy PE, Tolia NH. A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine. Immunity. 2023 Feb 14;56(2):433-443.e5. PMID:36792576 doi:10.1016/j.immuni.2023.01.012