Person:
García Linares, Sara

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First Name
Sara
Last Name
García Linares
URI
https://hdl.handle.net/20.500.14352/85452
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Bioquímica y Biología Molecular
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2015 - 201922020 - 20211
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Now showing 1 - 3 of 3
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    Structural foundations of sticholysin functionality
    (BBA - Proteins and Proteomics, 2021) Palacios Ortega, Juan; García Linares, Sara; Rivera de Torre, Esperanza; Heras Márquez, Diego; Gavilanes, José G.; Peter, Slotte; Martínez del Pozo, Álvaro
    Actinoporins constitute a family of α pore-forming toxins produced by sea anemones. The soluble fold of these proteins consists of a β-sandwich flanked by two α-helices. Actinoporins exert their activity by specifically recognizing sphingomyelin at their target membranes. Once there, they penetrate the membrane with their N-terminal α-helices, a process that leads to the formation of cation-selective pores. These pores kill the target cells by provoking an osmotic shock on them. In this review, we examine the role and relevance of the structural features of actinoporins, down to the residue level. We look at the specific amino acids that play significant roles in the function of actinoporins and their fold. Particular emphasis is given to those residues that display a high degree of conservation across the actinoporin sequences known to date. In light of the latest findings in the field, the membrane requirements for pore formation, the effect of lipid composition, and the process of pore formation are also discussed.
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    Cholesterol stimulates and ceramide inhibits Sticholysin II-induced pore formation in complex bilayer membranes
    (BBA - Biochimica et Biophysica Acta, 2015) Alm, Ida; García Linares, Sara; Gavilanes, José G.; Martínez del Pozo, Álvaro; Slotte, J. Peter
    The pore forming capacity of Sticholysin II (StnII; isolated from Stichodactyla helianthus) in bilayer membranes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), palmitoylsphingomyelin (PSM) and either cholesterol or palmitoyl ceramide (PCer) has been examined. The aim of the study was to elucidate how the presence of differently ordered PSM domains affected StnII oligomerization and pore formation. Cholesterol is known to enhance pore formation by StnII, and our results confirmed this and provide kinetic information for the process. The effect of cholesterol on bilayer permeabilization kinetics was concentration-dependent. In the concentration regime used (2.5–10 nmol cholesterol in POPC:PSM 80:20 by nmol), cholesterol also increased the acyl chain order in the fluid PSM domain and thus decreased bilayer fluidity, suggesting that fluidity per se was not responsible for cholesterol's effect. Addition of PCer (2.5–10 nmol) to the POPC:PSM (80:20 by nmol) bilayers attenuated StnII-induced pore formation, again in a concentration-dependent fashion. This addition also led to the formation of a PCer-rich gel phase. Addition of cholesterol to PCer-containing membranes could partially reduce the inhibitory effect of PCer on StnII pore formation. We conclude that the physical state of PSM (as influenced by either cholesterol or PCer) affected StnII binding and pore formation under the conditions examined.
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    The Effect of Cholesterol on the Long-Range Network of Interactions Established among Sea Anemone Sticholysin II Residues at the Water-Membrane Interface
    (Marine Drugs, 2015) García Linares, Sara; Alm, Ida; Maula, Terhi; Gavilanes Franco, José Gregorio; Slotte, J. Peter; Martínez Del Pozo, Álvaro
    Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol.