Kinetic Models of Secondary Active Transporters

Burtscher, Verena; Schicker, Klaus; Freissmuth, Michael; Sandtner, Walter

doi:10.3390/ijms20215365

Cited by 25 publications

(30 citation statements)

References 47 publications

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“…Also systematic analysis of the relationship between lipid composition, transport activity and dynamics (for instance by single molecule FRET methods [18,54]) will shed further light on the interplay between bilayer and protein. The gating behaviour might affect the order of binding and release of coupled ions and a substrate, and steady state and pre-steady state kinetic measurements may allow insight in the consequences of using one or two gates [55][56][57][58][59][60][61].…”

mentioning

confidence: 99%

Elevator-type mechanisms of membrane transport

Garaeva

Slotboom

2020

Biochemical Society Transactions

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Membrane transporters are integral membrane proteins that mediate the passage of solutes across lipid bilayers. These proteins undergo conformational transitions between outward- and inward-facing states, which lead to alternating access of the substrate-binding site to the aqueous environment on either side of the membrane. Dozens of different transporter families have evolved, providing a wide variety of structural solutions to achieve alternating access. A sub-set of structurally diverse transporters operate by mechanisms that are collectively named ‘elevator-type’. These transporters have one common characteristic: they contain a distinct protein domain that slides across the membrane as a rigid body, and in doing so it ‘drags” the transported substrate along. Analysis of the global conformational changes that take place in membrane transporters using elevator-type mechanisms reveals that elevator-type movements can be achieved in more than one way. Molecular dynamics simulations and experimental data help to understand how lipid bilayer properties may affect elevator movements and vice versa.

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mentioning

confidence: 99%

Elevator-type mechanisms of membrane transport

Garaeva

Slotboom

2020

Biochemical Society Transactions

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“…In reality, secondary active transporters frequently function in ways that are more complex and require a comprehensive reaction schemes for faithful representation of transporter function. For instance, some utilize additional co-substrates such as chloride or potassium [ 9 , 10 ], while some may bind substrates and co-substrates in a random rather than a sequential order [ 11 , 12 ] or some may display ionic slippage [ 13 , 14 ]. In addition, many transporters are voltage-dependent.…”

Section: Resultsmentioning

confidence: 99%

Descriptors of Secondary Active Transporter Function and How They Relate to Partial Reactions in the Transport Cycle

et al. 2021

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Plasmalemmal solute carriers (SLCs) gauge and control solute abundance across cellular membranes. By virtue of this action, they play an important role in numerous physiological processes. Mutations in genes encoding the SLCs alter amino acid sequence that often leads to impaired protein function and onset of monogenic disorders. To understand how these altered proteins cause disease, it is necessary to undertake relevant functional assays. These experiments reveal descriptors of SLC function such as the maximal transport velocity (Vmax), the Michaelis constant for solute uptake (KM), potencies for inhibition of transporter function (IC50/EC50), and many more. In several instances, the mutated versions of different SLC transporters differ from their wild-type counterparts in the value of these descriptors. While determination of these experimental parameters can provide conjecture as to how the mutation gives rise to disease, they seldom provide any definitive insights on how a variant differ from the wild-type transporter in its operation. This is because the experimental determination of association between values of the descriptors and several partial reactions a transporter undergoes is casual, but not causal, at best. In the present study, we employ kinetic models that allow us to derive explicit mathematical terms and provide experimental descriptors as a function of the rate constants used to parameterize the kinetic model of the transport cycle. We show that it is possible to utilize these mathematical expressions to deduce, from experimental outcomes, how the mutation has impinged on partial reactions in the transport cycle.

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“…The elevator-transport mechanisms are based on the presence of two distinct core and scaffold (or gate) domains in transporters (highlighted in magenta and deep blue, respectively, in Figure 3 ) that slide across each other in the membrane as independent rigid bodies and pull the permeated solute inside a cavity. One important aspect of SLCs are opening and closing events of the scaffold domain that opens at the opposite sides of a membrane, so their gates must work in a synchronised manner; these opening and closing events may operate on millisecond time scales as defined in a kinetic model [ 63 ]. For BOR1 and Bot1 SLC4 transporters, this provides alternating access via core domains that carry borate anions across a membrane [ 58 ].…”

Section: Structural Mechanisms Of Transporters Involved In B Toxicitymentioning

confidence: 99%

Plant transporters involved in combating boron toxicity: beyond 3D structures

Hrmová

Gilliham

Tyerman

2020

Biochemical Society Transactions

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Membrane transporters control the movement and distribution of solutes, including the disposal or compartmentation of toxic substances that accumulate in plants under adverse environmental conditions. In this minireview, in the light of the approaching 100th anniversary of unveiling the significance of boron to plants (K. Warington, 1923; Ann. Bot.37, 629) we discuss the current state of the knowledge on boron transport systems that plants utilise to combat boron toxicity. These transport proteins include: (i) nodulin-26-like intrinsic protein-types of aquaporins, and (ii) anionic efflux (borate) solute carriers. We describe the recent progress made on the structure–function relationships of these transport proteins and point out that this progress is integral to quantitative considerations of the transporter's roles in tissue boron homeostasis. Newly acquired knowledge at the molecular level has informed on the transport mechanics and conformational states of boron transport systems that can explain their impact on cell biology and whole plant physiology. We expect that this information will form the basis for engineering transporters with optimised features to alleviate boron toxicity tolerance in plants exposed to suboptimal soil conditions for sustained food production.

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Kinetic Models of Secondary Active Transporters

Cited by 25 publications

References 47 publications

Elevator-type mechanisms of membrane transport

Elevator-type mechanisms of membrane transport

Descriptors of Secondary Active Transporter Function and How They Relate to Partial Reactions in the Transport Cycle

Plant transporters involved in combating boron toxicity: beyond 3D structures

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