1rj7

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1rj7, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of EDA-A1

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The protective antigen (PA) moiety of anthrax toxin transports edema, factor and lethal factor to the cytosol of mammalian cells by a mechanism, that depends on its ability to oligomerize and form pores in the endosomal, membrane. Previously, some mutated forms of PA, designated dominant, negative (DN), were found to coassemble with wild-type PA and generate, defective heptameric pore-precursors (prepores). Prepores containing DN-PA, are impaired in pore formation and in translocating edema factor and, lethal factor across the endosomal membrane. To create a more, comprehensive map of sites within PA where a single amino acid replacement, can give a DN phenotype, we used automated systems to generate a, Cys-replacement mutation for each of the 568 residues of PA63, the active, 63-kDa proteolytic fragment of PA. Thirty-three mutations that reduced, PA's ability to mediate toxicity at least 100-fold were identified in all, four domains of PA63. A majority (22) were in domain 2, the pore-forming, domain. Seven of the domain-2 mutations, located in or adjacent to the, 2beta6 strand, the 2beta7 strand, and the 2beta10-2beta11 loop, gave the, DN phenotype. This study demonstrates the feasibility of high-throughput, scanning mutagenesis of a moderate sized protein. The results show that DN, mutations cluster in a single domain and implicate 2beta6 and 2beta7, strands and the 2beta10-2beta11 loop in the conformational rearrangement, of the prepore to the pore. They also add to the repertoire of mutations, available for structure-function studies and for designing new antitoxic, agents for treatment of anthrax.

Disease

Known diseases associated with this structure: Ectodermal dysplasia-1, anhidrotic OMIM:[300451], Hypodontia, X-linked OMIM:[300451]

About this Structure

1RJ7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis., Mourez M, Yan M, Lacy DB, Dillon L, Bentsen L, Marpoe A, Maurin C, Hotze E, Wigelsworth D, Pimental RA, Ballard JD, Collier RJ, Tweten RK, Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13803-8. Epub 2003 Nov 17. PMID:14623961

Page seeded by OCA on Mon Nov 12 19:04:20 2007