Lisa J Lapidus

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This review describes how kinetic experiments using techniques with dramatically improved time resolution have contributed to understanding mechanisms in protein folding. Optical triggering with nanosecond laser pulses has made it possible to study the fastest-folding proteins as well as fundamental processes in folding for the first time. These include(More)
Formation of a specific contact between two residues of a polypeptide chain is an important elementary process in protein folding. Here we describe a method for studying contact formation between tryptophan and cysteine based on measurements of the lifetime of the tryptophan triplet state. With tryptophan at one end of a flexible peptide and cysteine at the(More)
In plants, sterols play fundamental roles as membrane constituents in the biosynthesis of steroid hormones, and act as precursors for cell wall deposition. Sterols are synthesized in the endoplasmic reticulum (ER), but mainly accumulate in the plasma membrane. How sterols are trafficked in plant cells is largely unknown. In non-plant systems,(More)
One of the most recurring questions in protein folding refers to the interplay between formation of secondary structure and hydrophobic collapse. In contrast with secondary structure, it is hard to isolate hydrophobic collapse from other folding events. We have directly measured the dynamics of protein hydrophobic collapse in the absence of competing(More)
We describe a new, time-apertured photon correlation method for resolving the transition time between two states of RNA in folding--i.e., the time of the transition between states rather than the time spent in each state. Single molecule fluorescence resonance energy transfer and fluorescence correlation spectroscopy are used to obtain these measurements.(More)
We demonstrate that the sub-millisecond protein folding process referred to as "collapse" actually consists of at least two separate processes. We observe the UV fluorescence spectrum from naturally occurring tryptophans in three well-studied proteins, cytochrome c, apomyoglobin, and lysozyme, as a function of time in a microfluidic mixer with a dead time(More)
Quenching of the triplet state of tryptophan by close contact with cysteine has been used to measure the reaction-limited and diffusion-limited rates of loop formation in disordered polypeptides having the sequence cys-(ala-gly-gln)j-trp (j=1-9). The decrease in the length-dependence of the reaction-limited rate for short chains in aqueous buffer,(More)
By exploring the folding pathways of the B1 domain of protein L with a series of equilibrium and rapid kinetic experiments, we have found its unfolded state to be more complex than suggested by two-state folding models. Using an ultrarapid mixer to initiate protein folding within approximately 2-4 microseconds, we observe folding kinetics by intrinsic(More)
Enzyme-free electrochemical sensors enable rapid, high sensitivity measurements without the limitations associated with enzyme reporters. However, the performance of non-enzymatic electrochemical sensors tends to suffer from slow electrode kinetics and poor signal stability. We report a new enzyme-free electrochemical immunosensor based on a unique(More)
Recent work on α-synuclein has shown that aggregation is controlled kinetically by the rate of reconfiguration of the unstructured chain, such that the faster the reconfiguration, the slower the aggregation. In this work we investigate this relationship by examining α-synuclein in the presence of a small molecular tweezer, CLR01, which binds selectively to(More)