Recombinant proteins containing a short stretch of contiguous histidine residues (similar to 6) (''a His-tag'') can be specifically bound to N-nitrilotriacetic-acid-chelated nickel ions, providing a convenient general method for their purification. A lipid derivatized with a nickel-chelating head group may provide a general approach to two-dimensional crystallization of the His-tagged proteins, using the lipid layer technique. We have designed a synthetic phospholipid that carries a chelated nickel ion (Ni-NTA-DOPE). His-tagged recombinant HIV-1 reverse transcriptase (HIV-RT) bound specifically to lipid layers containing Ni-NTA-DOPE and formed crystals within minutes from a dilute protein solution. Two-dimensional crystals preserved in negative stain diffracted strongly to similar to 21 Angstrom. The projection map computed from averaged Fourier transforms revealed a structure similar in size and shape to a selected projection view of the 3-D structure that was previously determined for HIV-RT by X-ray crystallography. (C) 1994 Academic Press, Inc.