Interactions of Histone H1 with Phospholipids and Comparison of Its Binding to Giant Liposomes and Human Leukemic T Cells

• Published in: Biochemistry (Easton) Vol. 43; no. 31; pp. 10192 - 10202
• Main Authors: Zhao, Hongxia, Bose, Shambhunath, Tuominen, Esa K. J, Kinnunen, Paavo K. J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10-08-2004
• Subjects: Animals; Brain Chemistry; Cattle; Histones - chemistry; Histones - metabolism; Humans; Jurkat Cells; Leukemia, T-Cell - metabolism; Light; Liposomes - metabolism; Membrane Fusion; Microscopy, Interference; Microscopy, Phase-Contrast; Phosphatidylcholines - metabolism; Phosphatidylserines - metabolism; Phospholipids - metabolism; Protein Binding; Protein Structure, Secondary; Scattering, Radiation
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi049758b

Due to its net positive charge histone H1 readily associates with liposomes containing acidic phospholipids, such as phosphatidylserine (PS). Interestingly, circular dichroism reveals that while histone H1 in aqueous solutions appears as a random coil, its binding to liposomes containing PS is associated with a pronounced increase in α-helicity and β-sheet content, estimated at 7% and 24%, respectively. This interaction further results in vesicle aggregation and lipid mixing. Fluorescence microscopy revealed rapid binding of Texas Red-labeled H1 (TR-H1) to giant liposomes composed of phosphatidylcholine and PS (SOPC/brain PS, 9/1 molar ratio), followed by lateral segregation and subsequent translocation of the membrane-bound H1 into the giant liposome. The above processes in giant liposomes did depend on the presence of the negatively charged PS. Comparison of the behavior of H1 in giant liposomes to that in cultured leukemic T cells demonstrated very similar patterns. More specifically, fluorescence microscopy revealed binding of TR-H1 to the plasma membrane as lateral segregated microdomains, followed by translocation into the cell. H1 also triggered membrane blebbing and fragmentation of the nuclei of these cells, thus suggesting induction of apoptosis. Our findings indicate that histone H1 and acidic phospholipids form supramolecular aggregates in the plasma membrane of T cells, subsequently resulting in major rearrangements of cellular membranes. Our results allow us to conclude that the minimal requirement for the interaction of histone H1 with the leukemia cell plasma membrane is reproduced by giant liposomes composed of unsaturated phosphatidylcholine and phosphatidylserine, the latter being mandatory for the observed changes in the secondary structure of H1 as well as the macroscopic consequences of the H1−PS interactions.