Structural investigations of human A2M identify a hollow native conformation that underlies its distinctive protease-trapping mechanism
SL Harwood, J Lyngsø, A Zarantonello, K Kjøge… - Molecular & Cellular …, 2021 - ASBMB
Abstract Human α 2-macroglobulin (A2M) is the most characterized protease inhibitor in the
alpha-macroglobulin (αM) superfamily, but the structure of its native conformation has not …
alpha-macroglobulin (αM) superfamily, but the structure of its native conformation has not …
Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family
A2ML1 is a monomeric protease inhibitor belonging to the A2M superfamily of protease
inhibitors and complement factors. Here, we investigate the protease-inhibitory mechanism …
inhibitors and complement factors. Here, we investigate the protease-inhibitory mechanism …
Development of selective protease inhibitors via engineering of the bait region of human α2-macroglobulin
SL Harwood, NS Nielsen, K Diep, KT Jensen… - Journal of Biological …, 2021 - ASBMB
Human α 2-macroglobulin (A2M) is an abundant protease inhibitor in plasma, which
regulates many proteolytic processes and is involved in innate immunity. A2M's unique …
regulates many proteolytic processes and is involved in innate immunity. A2M's unique …
Substituting the thiol ester of human A2M or C3 with a disulfide produces native proteins with altered proteolysis-induced conformational changes
SL Harwood, NS Nielsen, H Pedersen, K Kjøge… - Biochemistry, 2020 - ACS Publications
Most proteins in the α-macroglobulin (αM) superfamily contain reactive thiol esters that are
required for their biological function. Here, we have characterized the human α2 …
required for their biological function. Here, we have characterized the human α2 …
Proteolytic cleavage of the TGF β co‐receptor CD 109 changes its conformation, resulting in protease inhibition via activation of its thiol ester, and dissociation from the …
KT Jensen, NS Nielsen, A Viana Almeida… - The FEBS …, 2024 - Wiley Online Library
The glycosylphosphatidylinositol (GPI)‐anchored protein cluster of differentiation 109
(CD109) is expressed on many human cell types and modulates the transforming growth …
(CD109) is expressed on many human cell types and modulates the transforming growth …
The conformational change of the protease inhibitor α2-macroglobulin is triggered by the retraction of the cleaved bait region from a central channel
SL Harwood, K Diep, NS Nielsen, KT Jensen… - Journal of Biological …, 2022 - ASBMB
The protease inhibitor α 2-macroglobulin (A2M) is a member of the ancient α 2-
macroglobulin superfamily (A2MF), which also includes structurally related proteins, such as …
macroglobulin superfamily (A2MF), which also includes structurally related proteins, such as …
Engineering New Protease Inhibitors Using α2-Macroglobulin
SL Harwood, JJ Enghild - Proteases and Cancer: Methods and Protocols, 2023 - Springer
Protease inhibitors of the alpha-macroglobulin family (αM) have a unique mechanism that
allows them to trap proteases that is dependent not on the protease's class, but rather on its …
allows them to trap proteases that is dependent not on the protease's class, but rather on its …