6QU9

Fab fragment of an antibody that inhibits polymerisation of alpha-1-antitrypsin

Summary for 6QU9

• Entry DOI: 10.2210/pdb6qu9/pdb
• EMDB information: 4620 4631 4632
• Descriptor: FAB 4B12 heavy chain, FAB 4B12 light chain, SULFATE ION, ... (6 entities in total)
• Functional Keywords: alpha-1 antitrypsin, z variant, polymers, protein aggregation, monoclonal antibody, fab fragment, copd, protease inhibitor, glycoprotein, deficiency, protein binding
• Biological source: Mus musculus (House mouse); More
• Total number of polymer chains: 4
• Total formula weight: 94115.64

Authors

Jagger, A.M.,Heyer-Chauhan, N.,Lomas, D.A.,Irving, J.A. (deposition date: 2019-02-26, release date: 2020-03-18, Last modification date: 2024-11-20)

Primary citation

Faull, S.V.,Elliston, E.L.K.,Gooptu, B.,Jagger, A.M.,Aldobiyan, I.,Redzej, A.,Badaoui, M.,Heyer-Chauhan, N.,Rashid, S.T.,Reynolds, G.M.,Adams, D.H.,Miranda, E.,Orlova, E.V.,Irving, J.A.,Lomas, D.A.
The structural basis for Z alpha 1 -antitrypsin polymerization in the liver.
Sci Adv, 6:-, 2020

PubMed Abstract: The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of α-antitrypsin as "polymer" chains in liver tissue. No detailed structural analysis has been performed of this material. Moreover, there is little information on the relevance of well-studied artificially induced polymers to these disease-associated molecules. We have isolated polymers from the liver tissue of Z α-antitrypsin homozygotes (E342K) who have undergone transplantation, labeled them using a Fab fragment, and performed single-particle analysis of negative-stain electron micrographs. The data show structural equivalence between heat-induced and ex vivo polymers and that the intersubunit linkage is best explained by a carboxyl-terminal domain swap between molecules of α-antitrypsin.

PubMed: 33087346
DOI: 10.1126/sciadv.abc1370

Experimental method

X-RAY DIFFRACTION (1.9 Å)