Membrane topology and insertion of membrane proteins: Search for topogenicsignals

Integral membrane proteins are found in all cellular membranes and carry ou t many of the functions that are essential to life. The membrane-embedded d omains of integral membrane proteins are structurally quite simple, allowin g the use of various prediction methods and biochemical methods to obtain s tructural information about membrane proteins. A critical step in the biosy nthetic pathway leading to the folded protein in the membrane is ifs insert ion into the lipid bilayer. Understanding of the fundamentals of the insert ion and folding processes will significantly improve the methods used to pr edict the three-dimensional membrane protein structure from the amino acid sequence. In the first part of this review, biochemical approaches to eluci date membrane protein topology are reviewed and evaluated, and in the secon d part, the use of similar techniques to study membrane protein insertion i s discussed. The latter studies search for signals in the polypeptide chain that direct the insertion process. Knowledge of the topogenic signals in t he nascent chain of a membrane protein is essential for the evaluation of m embrane topology studies.