Biomedical subjects

H R Treutlein

Publications and source records attributed to H R Treutlein.

21 records · Page 2Linked to original sources

PubMed1994

A dimerization motif for transmembrane alpha-helices.

Specific helix-helix interactions inside lipid bilayers guide the folding and assembly of many integral membrane proteins and their complexes. We report here a pattern of 7 amino acids (LIxxGVxxGVxxT) which when introduced into several hydrophobic transmembrane alpha-helices promotes their specific dimerization. Dimerization is driven by interactions that are specific, dominated by the helix-helix interface, and involve no potentially ionizable groups. The motif may provide a useful tool for the functional analysis of such interactions in a variety of systems. Further, since this particular motif is rare, whilst specific helix association is not, many other such motifs may exist, which could permit sorting within complex membranes as well as guiding folding and oligomerization.

Amino Acid Sequence↗

PubMed1992

Sequence specificity in the dimerization of transmembrane alpha-helices.

While several reports have suggested a role for helix-helix interactions in membrane protein oligomerization, there are few direct biochemical data bearing on this subject. Here, using mutational analysis, we show that dimerization of the transmembrane alpha-helix of glycophorin A in a detergent environment is spontaneous and highly specific. Very subtle changes in the side-chain structure at certain sensitive positions disrupt the helix-helix association. These sensitive positions occur at approximately every 3.9 residues along the helix, consistent with their comprising the interface of a closely fit transmembranous supercoil of alpha-helices. By contrast with other reported cases of interactions between transmembrane helices, the set of interfacial residues in this case contains no highly polar groups. Amino acids with aliphatic side chains define much of the interface, indicating that precise packing interactions between the helices may provide much of the energy for association. These data highlight the potential general importance of specific interactions between the hydrophobic anchors of integral membrane proteins.

Amino Acid Sequence↗

PubMed1992

The glycophorin A transmembrane domain dimer: sequence-specific propensity for a right-handed supercoil of helices.

Recent studies suggest specific roles for transmembrane helix association in a range of functions, but understanding of the conformation and energetics of these interactions has been elusive. We have studied the specific dimerization of the transmembrane helix of glycophorin A by calculating the minimized interaction energies of a large number of conformations using simulated annealing techniques and tested the models against mutational analysis data. We find that the dimer is best modeled as a right-handed supercoil with an extensive region of close packing along the dimer interface. Furthermore, we observe a sequence-specific propensity for a right-handed supercoil to form when starting the simulated annealing modeling from a dimer of helices with parallel axes, in contrast with the dimerization region of the transcription factor GCN4 which shows a high propensity for the more prevalent left-handed supercoiling.

Amino Acid Sequence↗