The structure of the predicted amino acid sequence in the FX domain of Photosystem 1 was studied by molecular modeling and a working hypothesis was developed for the functional interaction of PsaC with the core heterodimer. We propose that the intervening sequences between homologous cysteines in the FX cluster form two flexible loops and participate in the binding of PsaC, and that the arginine residues in the two surface-exposed loops may promote the interaction between the P700-FX core and the subunit. The model was tested experimentally; chemical modification of arginine residues in the P700-FX core using phenylglyoxal prevented reconstitution of the core with PsaC and PsaD after insertion of FeS clusters in vitro. Treatment of the P700-FX core with trypsin also prevented reconstitution of terminal electron transfer to FAFB, although neither treatments affected the electron transfer to FX as judged by flash kinetic spectrophotometry. Electron transfer in the P700-FAFB complex was not impaired by either phenylglyoxal or trypsin treatment indicating that the small subunit(s) protect the arginine residues that become chemically modified or cleaved. The data are consistent with the working model and point to additional experiments designed to identify the specific residues involved in the interaction between the P700-FX core and PsaC.