Investigating the conformational landscape of human histidine-rich glycoprotein using amide HDX-MS.

ABSTRACT: Histidine-rich glycoprotein (HRG) is a multidomain plasma protein involved in immune modulation, angiogenesis, coagulation and fibrinolysis. Despite its broad biological relevance, structural investigations into HRG have yielded only limited information, with no experimentally resolved three-dimensional structures of the intact protein to date. In this study, we integrate hydrogen-deuterium exchange mass spectrometry (HDX-MS) with predictive insights from AlphaFold to map the conformational landscape of HRG in solution under near-native conditions. The N1/N2 domains displayed low solvent exchange overall. However, specific regions of high-solvent exchange were also apparent, providing evidence for more dynamic stretches of secondary structure and the presence of flexible loops within these

SUBMITTER: Hierons SJ 

PROVIDER: S-EPMC12751054 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature