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Jeff Abramson

Publications and source records attributed to Jeff Abramson.

8 recordsLinked to original sources
PubMed2006

The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif.

The Na+/Ca2+ exchanger is a plasma membrane protein that regulates intracellular Ca2+ levels in cardiac myocytes. Transport activity is governed by Ca2+, and the primary Ca2+ sensor (CBD1) is located in a large cytoplasmic loop connecting two transmembrane helices. The binding of Ca2+ to the CBD1 sensory domain results in conformational changes that stimulate the exchanger to extrude Ca2+. Here, we present a crystal structure of CBD1 at 2.5A resolution, which reveals a novel Ca2+ binding site consisting of four Ca2+ ions arranged in a tight planar cluster. This intricate coordination pattern for a Ca2+ binding cluster is indicative of a highly sensitive Ca2+ sensor and may represent a general platform for Ca2+ sensing.

Animals↗
PubMed2004

Structural comparison of lactose permease and the glycerol-3-phosphate antiporter: members of the major facilitator superfamily.

Structural knowledge of the major facilitator superfamily has dramatically increased during the past year with the emergence of the structures of three members of this family of transporters. All three structures reveal 12 transmembrane helices forming two distinct domains, and could imply that members of this superfamily have preserved both secondary and tertiary structure elements during evolution.

Binding Sites↗
PubMed2003

The lactose permease of Escherichia coli: overall structure, the sugar-binding site and the alternating access model for transport.

Membrane transport proteins transduce free energy stored in electrochemical ion gradients into a concentration gradient and are a major class of membrane proteins, many of which play important roles in human health and disease. Recently, the X-ray structure of the Escherichia coli lactose permease (LacY), an intensively studied member of a large group of related membrane transport proteins, was solved at 3.5 A. LacY is composed of N- and C-terminal domains, each with six transmembrane helices, symmetrically positioned within the molecule. The structure represents the inward-facing conformation, as evidenced by a large internal hydrophilic cavity open to the cytoplasmic side. The structure with a bound lactose homolog reveals the sugar-binding site in the cavity, and a mechanism for translocation across the membrane is proposed in which the sugar-binding site has alternating accessibility to either side of the membrane.

Binding Sites↗
PubMed2003

Structure and mechanism of the lactose permease of Escherichia coli.

Membrane transport proteins that transduce free energy stored in electrochemical ion gradients into a concentration gradient are a major class of membrane proteins. We report the crystal structure at 3.5 angstroms of the Escherichia coli lactose permease, an intensively studied member of the major facilitator superfamily of transporters. The molecule is composed of N- and C-terminal domains, each with six transmembrane helices, symmetrically positioned within the permease. A large internal hydrophilic cavity open to the cytoplasmic side represents the inward-facing conformation of the transporter. The structure with a bound lactose homolog, beta-D-galactopyranosyl-1-thio-beta-D-galactopyranoside, reveals the sugar-binding site in the cavity, and residues that play major roles in substrate recognition and proton translocation are identified. We propose a possible mechanism for lactose/proton symport (co-transport) consistent with both the structure and a large body of experimental data.

Amino Acid Substitution↗
PubMed2002

The X-ray crystal structures of wild-type and EQ(I-286) mutant cytochrome c oxidases from Rhodobacter sphaeroides.

The structure of cytochrome c oxidase from Rhodobacter sphaeroides has been solved at 2.3/2.8A (anisotropic resolution). This high-resolution structure revealed atomic details of a bacterial terminal oxidase including water molecule positions and a potential oxygen pathway, which has not been reported in other oxidase structures. A comparative study of the wild-type and the EQ(I-286) mutant enzyme revealed structural rearrangements around E(I-286) that could be crucial for proton transfer in this enzyme. In the structure of the mutant enzyme, EQ(I-286), which cannot transfer protons during oxygen reduction, the side-chain of Q(I-286) does not have the hydrogen bond to the carbonyl oxygen of M(I-107) that is seen in the wild-type structure. Furthermore, the Q(I-286) mutant has a different arrangement of water molecules and residues in the vicinity of the Q side-chain. These differences between the structures could reflect conformational changes that take place upon deprotonation of E(I-286) during turnover of the wild-type enzyme, which could be part of the proton-pumping machinery of the enzyme.

Binding Sites↗
PubMed2001

Purification and crystallization of the respiratory complex formate dehydrogenase-N from Escherichia coli.

A membrane-protein complex, formate dehydrogenase-N from Escherichia coli, has been purified and crystallized. This molybdenum-containing enzyme, composed of alpha, beta and gamma subunits, is the major electron donor to the nitrate respiratory chain of E. coli. The formate dehydrogenase-N crystals belong to the cubic space group P2(1)3, with unit-cell parameters a = b = c = 203 A. An asymmetric unit of the crystals is assumed to contain one formate dehydrogenase-N monomer (MW 170 kDa). One data set to 1.6 A resolution, with 342 711 independent observations (94.4% complete) and an R(merge) of 0.08, has been collected from a single crystal. This is the highest resolution data set reported for a membrane-protein complex to date.

Crystallization↗
PubMedDate not supplied

Lactose permease as a paradigm for membrane transport proteins (Review).

Our structural knowledge of the major facilitator superfamily (MFS) has dramatically increased in the past year with three structures of proteins from the MFS (oxalate/formate antiporter; lactose/proton symporter and the P(i)/glycerol-3-phosphate antiporter). All three structures revealed 12 transmembrane helices forming two distinct domains and could imply that members of the MFS have preserved both secondary as well as tertiary structural elements during evolution. Lactose permease, a particularly well-studied member of the MFS, has been extensively explored by a number of molecular biological, biochemical and biophysical approaches. In this review, we take a closer look at the structure of LacY and incorporate a wealth of biochemical and biophysical data in order to propose a possible mechanism for lactose/proton symport. In addition, we make some brief comparisons between the structures of LacY and GlpT.

Animals↗