Isaiah T. Arkin

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One of the central paradigms of structural biology is that membrane proteins are "inside-out" proteins, in that they have a core of polar residues surrounded by apolar residues. This is the reverse of the characteristics found in water-soluble proteins. We have decided to test this paradigm, now that sufficient numbers of transmembrane alpha-helical(More)
Phospholamban is a 52 amino acid residue membrane protein involved with the regulation of calcium levels across sarcoplasmic reticulum membranes in cardiac muscle cells. The N-terminal 30 amino acid residues of the protein are largely hydrophilic and include two sites whose phosphorylation is thought to dissociate an inhibitory complex between phospholamban(More)
The structures of membrane transporters are still mostly unsolved. Only recently, the first two high-resolution structures of transporters of the major facilitator superfamily (MFS) were published. Despite the low sequence similarity of the two proteins involved, lactose permease and glycerol-3-phosphate transporter, the reported structures are highly(More)
Syntaxin 1A (Sx1A) modifies the activity of voltage-gated Ca2+ channels acting via the cytosolic and the two vicinal cysteines (271 and 272) at the transmembrane domain. Here we show that Sx1A modulates the Lc-type Ca2+ channel, Cav1.2, in a cooperative manner, and we explore whether channel clustering or the Sx1A homodimer is responsible for this activity.(More)
Increasing evidence suggests that membrane-embedded hydrophobic segments can interact within the phospholipid milieu of the membrane with varying degrees of specificity and thus contribute to the folding and oligomerization of proteins. We have used synthetic peptides corresponding to segments from the hydrophobic core of the Shaker potassium channel as a(More)
Aquaporin 0 (AQP0), the most abundant membrane protein in mammalian lens fiber cells, not only serves as the primary water channel in this tissue but also appears to mediate the formation of thin junctions between fiber cells. AQP0 is remarkably less water permeable than other aquaporins, but the structural basis and biological significance of this low(More)
Vpu is an 81 amino acid auxiliary protein in HIV-1 which exhibits channel activity. We used two homo-pentameric bundles with the helical transmembrane segments derived from FTIR spectroscopy in combination with a global molecular dynamics search protocol: (i) tryptophans (W) pointing into the pore, and (ii) W facing the lipids. Two equivalent bundles have(More)
Fast protein dynamics can be missed with techniques that have relatively slow observation times. Using 2D IR spectroscopy and isotope labeling, we have probed the rapid, picosecond dynamics of a membrane protein in its native environment. By measuring the homogeneous and inhomogeneous IR linewidths of 11 amide I modes (backbone carbonyl stretch), we have(More)
SUMMARY The genomic abundance and pharmacological importance of membrane proteins have fueled efforts to identify them based solely on sequence information. Previous methods based on the physicochemical principle of a sliding window of hydrophobicity (hydropathy analysis) have been replaced by approaches based on hidden Markov models or neural networks(More)