Recent Progress in the Topology, Structure, and Oligomerization of Caveolin: A Building Block of Caveolae

Root, Kyle T.; Plucinsky, Sarah M.; Glover, Kerney Jebrell

doi:10.1016/bs.ctm.2015.03.007

Cited by 44 publications

(47 citation statements)

References 105 publications

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“…2b). It is worth mentioning that Cav-1 is a ~22 kDa integral membrane protein that do not span the lipid bilayer completely and instead is inserted into the inner leaflet of the plasma membrane adopting a hairpin-like structure, with both the N- and C- termini facing the cytoplasm 25 . These control experiments indicated that PK was only able to degrade proteins present in the plasma membrane and exposed to the extracellular space.…”

Section: Resultsmentioning

confidence: 99%

Human Sialidase Neu3 is S-Acylated and Behaves Like an Integral Membrane Protein

Rodríguez-Walker

Daniotti

2017

Sci Rep

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Membrane-bound sialidase Neu3 is involved in the catabolism of glycoconjugates, and plays crucial roles in numerous biological processes. Since the mechanism of its association with membranes is still not completely understood, the aim of this work was to provide further information regarding this aspect. Human Neu3 was found to be associated with the plasma membrane and endomembranes, and it was not released from the lipid bilayer under conditions that typically release peripheral membrane proteins. By different experimental approaches, we demonstrated that its C-terminus is exposed to the cytosol while another portion of the protein is exposed to the extracellular space, suggesting that Neu3 possesses the features of a transmembrane protein. However, in silico analysis and homology modeling predicted that the sialidase does not contain any α-helical transmembrane segment and shares the same β-propeller fold typical of viral and bacterial sialidases. Additionally, we found that Neu3 is S-acylated. Since this post-translational modification is restricted to the cytosolic side of membranes, this finding strongly supports the idea that Neu3 may contain a cytosolic-exposed domain. Although it remains to be determined exactly how this sialidase crosses the lipid bilayer, this study provides new insights about membrane association and topology of Neu3.

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Section: Resultsmentioning

confidence: 99%

Human Sialidase Neu3 is S-Acylated and Behaves Like an Integral Membrane Protein

Rodríguez-Walker

Daniotti

2017

Sci Rep

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“…These caveolar complexes form a scaffold that compartmentalizes various signal transducers and regulate their cellular trafficking and activity (7,8). Because of its central role in cell signaling, cav-1 has been implicated in cancer (9) as well as in a wide range of other diseases such as diabetes, muscular degenerative disorders, atherosclerosis, and pulmonary fibrosis (10). An interesting feature of the cav-1 protein is that it is palmitoylated on three cysteine residues at the C-terminal by the reversible attachment of a 16-carbon acyl chain via a thioester bond.…”

Section: Introductionmentioning

confidence: 99%

Interplay between Membrane Curvature and Cholesterol: Role of Palmitoylated Caveolin-1

Krishna

Sengupta

2019

Biophysical Journal

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Caveolin-1 (cav-1) is an important player in cell signaling and endocytosis that has been shown to colocalize with cholesterol-rich membrane domains. Experimental studies with varying cav-1 constructs have suggested that it can induce both cholesterol clustering and membrane curvature. Here, we probe the molecular origin of membrane curvature and cholesterol clustering by cav-1 by using coarse-grain molecular dynamics simulations. We have performed a series of simulations of a functionally important cav-1 construct, comprising the membrane-interacting domains and a C-terminal palmitoyl tail. Our results suggest that cav-1 is able to induce cholesterol clustering in the membrane leaflet to which it is bound as well as the opposing leaflet. A positive membrane curvature is observed upon cav-1 binding in cholesterol-containing bilayers. Interestingly, we observe an interplay between cholesterol clustering and membrane curvature such that cav-1 is able to induce higher membrane curvature in cholesterol-rich membranes. The role of the cav-1 palmitoyl tail is less clear and appears to increase the membrane contacts. Further, we address the importance of the secondary structure of cav-1 domains and show that it could play an important role in membrane curvature and cholesterol clustering. Our work is an important step toward a molecular picture of caveolae and vesicular endocytosis.

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“…Caveolin proteins are traditionally divided into four structural domains: a flexible N-terminal domain (residues 1-54), a caveolin scaffolding domain (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74), a membrane embedded domain (75-106), and a C-terminal cytosolic domain (107-151) (21). The cytosolic N-terminal domain contains a highly conserved caveolin signature motif (residues 41-48, FEDVIAEP).…”

Section: Introductionmentioning

confidence: 99%

A pH-Mediated Topological Switch within the N-Terminal Domain of Human Caveolin-3

Kim

Schlebach

et al. 2016

Biophysical Journal

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Caveolins mediate the formation of caveolae, which are small omega-shaped membrane invaginations involved in a variety of cellular processes. There are three caveolin isoforms, the third of which (Cav3) is expressed in smooth and skeletal muscles. Mutations in Cav3 cause a variety of human muscular diseases. In this work, we characterize the secondary structure, dynamics, and topology of the monomeric form of the full-length lipidated protein. Cav3 consists of a series of membrane-embedded or surface-associated helical elements connected by extramembrane connecting loops or disordered domains. Our results also reveal that the N-terminal domain undergoes a large scale pH-mediated topological rearrangement between soluble and membrane-anchored forms. Considering that roughly one-third of pathogenic mutations in Cav3 influence charged residues located in this domain, we hypothesize that this transition is likely to be relevant to the molecular basis of Cav3-linked diseases. These results provide insight into the structure of Cav3 and set the stage for mechanistic investigations of the effects of pathogenic mutations.

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Recent Progress in the Topology, Structure, and Oligomerization of Caveolin: A Building Block of Caveolae

Cited by 44 publications

References 105 publications

Human Sialidase Neu3 is S-Acylated and Behaves Like an Integral Membrane Protein

Human Sialidase Neu3 is S-Acylated and Behaves Like an Integral Membrane Protein

Interplay between Membrane Curvature and Cholesterol: Role of Palmitoylated Caveolin-1

A pH-Mediated Topological Switch within the N-Terminal Domain of Human Caveolin-3

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