Sarco-endoplasmic reticulum calcium transporting ATPase expressed in adult fast-twitch skeletal muscle (SERCA1a) utilizes energy from ATP hydrolysis to transport Ca²⁺ from cytoplasm into sarcoplasmic reticulum against the Ca² concentration gradient. By this means, the Ca² concentration in cytoplasm may decrease and contracted muscle cells relax. SERCA1a is the structurally and functionally best studied representative of the P-type ion transporting ATPase. Studies of SERCA1a may provide with enlightening information for research about other SERCA isoforms and P type ATPase. To understand the functional roles of the linker between the transmembrane helix M7 and the transmembrane helix M8 (L78), mutational studies about some L78 amino acid residues were performed to evaluate the effect of their single substitutions on the SERCA1a reaction cycle. Mutant SERCA1a cDNAs were obtained by Quick Change site directed mutagenesis. SERCA1a wild type and mutant proteins were expressed in COS-1 cells separately and extracted by microsome preparation. Single mutant SERCA1a proteins, wild type SERCA1a proteins and control microsomes were checked with radioactive [γ-³²P]ATP, ⁴⁵CaCl₂, and ³²Pi independently to determine their ATPase activities, Ca² transport rates, amount of total EP formed from ATP, and amount of E2P formed from Pi. Results showed that all single mutants except for G864A transported Ca² at lower rates than that of the SERCA1a wild type protein. Single mutations of G862 or P863 lead to severe decreases of the ATPase activity and the amount of EP formed from ATP or Pi. Measurements about ATP hydrolysis and EP formation of A893P gavde ata similar to those obtained from G⁸⁶² P⁸⁶³ single mutant proteins, whereas single mutants of G864 and FMQ873-875 did not induce significant reduction of ATPase activity and EP amount. Experimental results above indicated that L78 is involved in the Ca² transport across the endoplasmic reticulum membrane, and moreover, appropriate turns at GPG862-864 and near A893 are essential for D351 phosphorylation at the cytoplasmic domain P. Thereby it is suggested that the accurate configuration and flexibility of L78 play important roles for the successive conformational changes accompanying the SERCA1a reaction cycle.