1pln

Publication Abstract from PubMed

Molecular models of the transmembrane domain of the phospholamban pentamer have been generated by a computational method that uses the experimentally measured effects of systematic single-site mutations as a guiding force in the modeling procedure. This method makes the assumptions that 1) the phospholamban transmembrane domain is a parallel five-helix bundle, and 2) nondisruptive mutation positions are lipid exposed, whereas 3) disruptive or partially disruptive mutations are not. Our procedure requires substantially less computer time than systematic search methods, allowing rapid assessment of the effects of different experimental results on the helix arrangement. The effectiveness of the approach is investigated in test calculations on two helix-dimer systems of known structure. Two independently derived sets of mutagenesis data were used to define the restraints for generating models of phospholamban. Both resulting models are left-handed, highly symmetrical pentamers. Although the overall bundle geometry is very similar in the two models, the orientation of individual helices differs by approximately 50 degrees, resulting in different sets of residues facing the pore. This demonstrates how differences in restraints can have an effect on the model structures generated, and how the violation of these restraints can identify inconsistent experimental data.

Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban.,Herzyk P, Hubbard RE Biophys J. 1998 Mar;74(3):1203-14. PMID:9512019^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.