Impact of the S20G Mutation on the Structural and Aggregation Properties of hIAPP Monomers
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Type 2 diabetes (T2D), the predominant form of diabetes (>90% of cases), is characterized by human islet amyloid polypeptide (hIAPP) amyloid deposits resulting from protein misfolding. The serine-to-glycine mutation at position 20 (S20G) in hIAPP is associated with T2D in certain populations, yet its molecular impact on conformation and aggregation remains poorly understood. This study employs replica-exchange molecular dynamics (REMD) simulations to investigate how the S20G mutation, combined with histidine behaviors (tautomerism and protonation), influences hIAPP monomer structural and aggregation properties. We analyzed clustering, secondary structure, hydrogen bonds, and contact maps across three histidine states: hIAPP(ε), hIAPP(δ), and hIAPP(p). Our findings reveal distinct conformational tendencies, providing novel insights into the mechanisms underlying hIAPP misfolding in T2D.
Abstract
Type 2 diabetes (T2D), the predominant form of diabetes (>90% of cases), is characterized by human islet amyloid polypeptide (hIAPP) amyloid deposits resulting from protein misfolding. The serine-to-glycine mutation at position 20 (S20G) in hIAPP is associated with T2D in certain populations, yet its molecular impact on conformation and aggregation remains poorly understood. This study employs replica-exchange molecular dynamics (REMD) simulations to investigate how the S20G mutation, combined with histidine behaviors (tautomerism and protonation), influences hIAPP monomer structural and aggregation properties. We analyzed clustering, secondary structure, hydrogen bonds, and contact maps across three histidine states: hIAPP(ε), hIAPP(δ), and hIAPP(p). Our findings reveal distinct conformational tendencies, providing novel insights into the mechanisms underlying hIAPP misfolding in T2D.