3T1P
Crystal structure of an alpha-1-antitrypsin trimer
Summary for 3T1P
| Entry DOI | 10.2210/pdb3t1p/pdb |
| Descriptor | Alpha-1-antitrypsin (1 entity in total) |
| Functional Keywords | serpin, protease inhibitor, plasma, hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted. Short peptide from AAT: Secreted, extracellular space, extracellular matrix: P01009 |
| Total number of polymer chains | 1 |
| Total formula weight | 41842.86 |
| Authors | Huntington, J.A.,Yamasaki, M. (deposition date: 2011-07-22, release date: 2011-08-17, Last modification date: 2024-11-06) |
| Primary citation | Yamasaki, M.,Sendall, T.J.,Pearce, M.C.,Whisstock, J.C.,Huntington, J.A. Molecular basis of alpha 1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep., 12:1011-1017, 2011 Cited by PubMed Abstract: α(1)-Antitrypsin (α1AT) deficiency is a disease with multiple manifestations, including cirrhosis and emphysema, caused by the accumulation of stable polymers of mutant protein in the endoplasmic reticulum of hepatocytes. However, the molecular basis of misfolding and polymerization remain unknown. We produced and crystallized a trimeric form of α1AT that is recognized by an antibody specific for the pathological polymer. Unexpectedly, this structure reveals a polymeric linkage mediated by domain swapping the carboxy-terminal 34 residues. Disulphide-trapping and antibody-binding studies further demonstrate that runaway C-terminal domain swapping, rather than the s4A/s5A domain swap previously proposed, underlies polymerization of the common Z-mutant of α1AT in vivo. PubMed: 21909074DOI: 10.1038/embor.2011.171 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.9 Å) |
Structure validation
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