Crystal structure of saposin D in an open conformation

Gebai, A.; Gorelik, A.; Nagar, Bhushan

doi:10.1016/j.jsb.2018.07.011

Cited by 13 publications

(14 citation statements)

References 51 publications

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“…The latter assumes the preservation of the PSI in general after excision from the parent AP, however, the fate of the PSI post-targeting is unknown [29], and addresses the importance of the large number of hydrophobic interactions identified-up to 106 between monomeric units-which likely stabilizes the dimer interface. Similar dimer forms are seen in saposins A-D [18,[30][31][32].…”

Section: Plos Onesupporting

confidence: 64%

The role of disulfide bonds in a Solanum tuberosum saposin-like protein investigated using molecular dynamics

et al. 2020

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The Solanum tuberosum plant specific insert (StPSI) has a defensive role in potato plants, with the requirements of acidic pH and anionic lipids. The StPSI contains a set of three highly conserved disulfide bonds that bridge the protein's helical domains. Removal of these bonds leads to enhanced membrane interactions. This work examined the effects of their sequential removal, both individually and in combination, using all-atom molecular dynamics to elucidate the role of disulfide linkages in maintaining overall protein tertiary structure. The tertiary structure was found to remain stable at both acidic (active) and neutral (inactive) pH despite the removal of disulfide linkages. The findings include how the dimer structure is stabilized and the impact on secondary structure on a residue-basis as a function of disulfide bond removal. The StPSI possesses an extensive network of inter-monomer hydrophobic interactions and intra-monomer hydrogen bonds, which is likely the key to the stability of the StPSI by stabilizing local secondary structure and the tertiary saposin-fold, leading to a robust association between monomers, regardless of the disulfide bond state. Removal of disulfide bonds did not significantly impact secondary structure, nor lead to quaternary structural changes. Instead, disulfide bond removal induces regions of amino acids with relatively higher or lower variation in secondary structure, relative to when all the disulfide bonds are intact. Although disulfide bonds are not required to preserve overall secondary structure, they may have an important role in maintaining a less plastic structure within plant cells in order to regulate membrane affinity or targeting.

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Section: Plos Onesupporting

confidence: 64%

The role of disulfide bonds in a Solanum tuberosum saposin-like protein investigated using molecular dynamics

et al. 2020

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“…MOA studies have yet to be reported on the anionic class II bacteriocins. One testable hypothesis is that the MOA may involve lipid extraction and membrane solubilization, similar to the negatively charged saposin-like proteins. , …”

Section: Circular Bacteriocinsmentioning

confidence: 99%

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

et al. 2022

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a natural product class that has undergone significant expansion due to the rapid growth in genome sequencing data and recognition that they are made by biosynthetic pathways that share many characteristic features. Their mode of actions cover a wide range of biological processes and include binding to membranes, receptors, enzymes, lipids, RNA, and metals as well as use as cofactors and signaling molecules. This review covers the currently known modes of action (MOA) of RiPPs. In turn, the mechanisms by which these molecules interact with their natural targets provide a rich set of molecular paradigms that can be used for the design or evolution of new or improved activities given the relative ease of engineering RiPPs. In this review, coverage is limited to RiPPs originating from bacteria.

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“…We found that the Hill equation is appropriate for determining the K Dapp for liposome binding as it accounts for cooperativity upon binding [20]. SapC and many other saposin-like proteins are known to dimerize [21][22][23][24], suggesting that the Hill coefficient is necessary to account for multiple proteins binding to a single site. the KDapp (1.6 nM) [6].…”

Section: Expected Resultsmentioning

confidence: 99%

Quantitative Studies on the Interaction between Saposin-like Proteins and Synthetic Lipid Membranes

Sandin

Alba

2022

MPs

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Members of the saposin-fold protein family and related proteins sharing a similar fold (saposin-like proteins; SAPLIP) are peripheral-membrane binding proteins that perform essential cellular functions. Saposins and SAPLIPs are abundant in both plant and animal kingdoms, and peripherally bind to lipid membranes to play important roles in lipid transfer and hydrolysis, defense mechanisms, surfactant stabilization, and cell proliferation. However, quantitative studies on the interaction between proteins and membranes are challenging due to the different nature of the two components in relation to size, structure, chemical composition, and polarity. Using liposomes and the saposin-fold member saposin C (sapC) as model systems, we describe here a method to apply solution NMR and dynamic light scattering to study the interaction between SAPLIPs and synthetic membranes at the quantitative level. Specifically, we prove with NMR that sapC binds reversibly to the synthetic membrane in a pH-controlled manner and show the dynamic nature of its fusogenic properties with dynamic light scattering. The method can be used to infer the optimal pH for membrane binding and to determine an apparent dissociation constant (KDapp) for protein-liposome interaction. We propose that these experiments can be applied to other proteins sharing the saposin fold.

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Crystal structure of saposin D in an open conformation

Cited by 13 publications

References 51 publications

The role of disulfide bonds in a Solanum tuberosum saposin-like protein investigated using molecular dynamics

The role of disulfide bonds in a Solanum tuberosum saposin-like protein investigated using molecular dynamics

Mechanism of Action of Ribosomally Synthesized and Post-Translationally Modified Peptides

Quantitative Studies on the Interaction between Saposin-like Proteins and Synthetic Lipid Membranes

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