2msx

The solution structure of the MANEC-type domain from Hepatocyte Growth Factor Inhibitor 1 reveals an unexpected PAN/apple domain-type fold

spinqualitylabelsall models 2msx Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2msx is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SPIT1_HUMAN Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14). Publication Abstract from PubMed A decade ago, a Motif at N-terminus with Eight-Cysteines or in short MANEC was defined as a new protein domain family. This domain is found exclusively in the N-terminus of >400 multi-domain type-1 transmembrane proteins from animals. Despite the large number of MANEC-containing proteins, only one has been characterized at the protein level: hepatocyte growth factor activator inhibitor-1 (HAI-1). HAI-1 is an essential protein, as knockout mice die in utero due to placental defects. HAI-1 is an inhibitor of matriptase, hepsin and hepatocyte growth factor activator, all serine proteases with important roles in epithelial development, cell growth and homeostasis. Dysregulation of these proteases has been causatively implicated in pathological conditions such as skin diseases and cancer. Detailed functional understanding of HAI-1 and other MANEC-containing proteins is hampered by the lack of structural information on MANEC. Although many MANEC sequences exist, sequence-based database searches fail to predict structural homology. Here we present the NMR solution structure of the MANEC domain from HAI-1, the first three-dimensional structure from the MANEC domain family. Unexpectedly, MANEC is a new subclass of the PAN/apple domain family, with its own unifying features, such as two additional disulfide bonds, two extended loop regions and additional alpha-helical elements. As shown for other PAN/apple domain-containing proteins, we propose a similar active role of the MANEC domain in intramolecular and intermolecular interactions. The structure provides a tool for the further elucidation of HAI-1 function as well as a reference for the study of other MANEC-containing proteins. The solution structure of the MANEC-type domain from Hepatocyte Growth Factor Activator Inhibitor 1 reveals an unexpected PAN/apple domain-type fold.,Hong Z, Nowakowski M, Spronk C, Petersen SV, Andreasen PA, Kozminski W, Mulder FA, Jensen JK Biochem J. 2014 Dec 16. PMID:25510835 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hepatocyte growth factor activator inhibitor

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