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Tag Archives: membrane-protein
Borate transporter Bor1p appears to function according to the alternating access model

Borate transporter Bor1p appears to function according to the alternating access model

Bor1p is a secondary transporter in yeast that is responsible for boron transport, likely powered by the proton gradient across the cell membrane. By combining cryo-electron microscopy and MD simulations we could generate models of Bor1p in inward facing and outward facing conformation, which suggest rigid body movements of the core domain relative to the gate domain, consistent with a rocking-bundle transport mechanism.

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APS 4CS Meeting 2017

APS 4CS Meeting 2017

The APS 4 Corners Section Meeting is held annually and will be hosted at Colorado State University on October 20th and 21st. Oliver was invited to present the group’s research on Structure and function of electrogenic sodium/proton antiporter membrane proteins.

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The State Press featured the Lab

The State Press featured the Lab

ASU’s The State Press featured the work of the lab in the article ASU researchers use simulations where experiments fail. The article was based on an interview with lab members and the PI.

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Molecular basis of ion translocation in sodium/proton antiporters

Molecular basis of ion translocation in sodium/proton antiporters

We studied the process of sodium/proton antiport in the NapA transporter. Through a combination of X-ray crystallography, biochemistry and computer simulations we could show that the antiporter undergoes a large conformational transition that resembles a *elevator*-like movement whereby a single domain moves up- and down through the membrane and carries a sodium ion with it.

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Research Experience for Undergraduates (Summer 2015)

Research Experience for Undergraduates (Summer 2015)

The Beckstein Lab offers a fully funded ten-week research program in computational biophysics for a highly motivated undergraduate student. This is a NSF-sponsored Research Experience for Undergraduates. Deadline for applications is May 31, 2015.

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Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights

A new crystal structure of the Escherichia coli NhaA dimer reveals a previously unidentified salt bridge between two highly conserved residues at the putative binding site. The combination of structural data with molecular dynamics simulations yields new insights into the transport mechanism.

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Becksteinlab featured in A2C2 Quarterly

Becksteinlab featured in A2C2 Quarterly

The work in the lab was featured in the Winter 2014 edition of the A2C2 Quarterly newsletter.

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Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

Flexible Gates Generate Occluded Intermediates in the Transport Cycle of LacY

We show that one of the best-studied secondary active transporters, the lactose permease LacY, goes through an occluded conformation during its transport cycle. We propose an atomically detailed model of the apo-occluded state. The simulations predict the formation of a transient salt bridge that has been hypothesized in the canonical model for transport of LacY. The simulations are validated by comparison to experimental EPR DEER data, using a new approach to simulate spin-label distance distributions through post-processing of molecular dynamics trajectories. We also define a set of order parameters that consistently classify all known MFS transporter structures as outward-open, occluded, or inward-open conformations.

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Influence of lipids on transmembrane transport proteins

Influence of lipids on transmembrane transport proteins

We are reviewing the evidence for direct effects of lipids on the transport properties of ion channels and active transporters. For ion channels it has been convincingly shown that specific lipid-protein interactions can directly affect their function. For transporters, the evidence is more ambiguous. In all areas, however, the use of computer simulations extends the way in which we understand protein-membrane interactions.

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A two-domain elevator mechanism for sodium/proton antiport

A two-domain elevator mechanism for sodium/proton antiport

In a combined X-ray crystallography/biochemistry/molecular simulation study published in Nature we present the structure of the sodium/proton antiporter NapA in its outward facing conformation. Together with the inward facing conformation of the related transporter NhaA we can now understand the conformational changes required for the sodium/proton antiport mechanism.

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X-ray crystallography and Simulations

X-ray crystallography and Simulations

Structures of membrane proteins can be obtained by the experimental technique of X-ray crystallography. However, proteins are typically not crystallized in their native environment, the lipid membrane. Molecular dynamics simulations of the protein in the membrane provide a realistic model of the interactions between transporter and lipid bilayer.

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Long Liang

Long Liang

Long Liang majored in Biology in his undergraduate study, and shifted to Physics for his PhD study. He hopes to combine his background in Biology and Physics to understand life in terms of the more fundamental Physical laws. In his rotation project he worked on constructing a validated model of a human neurotransmitter transporter. Long is now part of the Complex Materials Group and works on his PhD under Professor Yang Jiao.

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The alternating access mechanism in Mhp1

The alternating access mechanism in Mhp1

Secondary transporters couple the free energy stored in an ionic gradient to the movement of solutes across the cell membrane. The coupling enables these transmembrane proteins to transport small molecules against their own concentration gradients. The transporters function by cycling between different conformational states in which access to the central binding site is switched from the extracellular solution to the intracellular compartment. Using experimental and computational approaches we could visualize for the first time how this process occurs for a secondary transporter.

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Simulations of membrane proteins

Simulations of membrane proteins

Many proteins in the living cell can be understood as molecular machines that use a source of energy to produce mechanical or chemical work. My lab’s primary interest is in those proteins located in the cell membrane that move nutrients, signalling molecules, or waste products into and out of the cell. We study their molecular mechanisms of action by detailed molecular dynamics simulations, which provide a “movie” of full atomic detail of a working protein.