There is a growing interest in understanding how hydrostatic pressure (P) impacts the thermodynamic stability (Delta G) of globular proteins. The pressure dependence of stability is defined by the change in volume upon denaturation, Delta V = (partial derivative Delta G/partial derivative P)(T). The temperature dependence of change in volume upon denaturation itself is defined by the changes in thermal expansivity (Delta E), Delta E = (partial derivative Delta V/partial derivative T)(P). The pressure perturbation calorimetry (PPC) allows direct experimental measurement of the thermal expansion coefficient, alpha = E/V, of a protein in the native, alpha(N)(T), and unfolded, alpha(U)(T), states as a function of temperature. We have shown previously that alpha(U)(T) is a nonlinear function of temperature but can be predicted well from the amino acid sequence using alpha(T) values for individual amino acids (J. Phys. Chem. B 2010, 114, 16166-16170). In this work, we report PPC results on a diverse set of nine proteins and discuss molecular factors that can potentially influence the thermal expansion coefficient, alpha(N)(T), and the thermal expansivity, E-N(T), of proteins in the native state. Direct experimental measurements by PPC show that alpha(N)(T) and E-N(T) functions vary significantly for different proteins. Using comparative analysis and site-directed mutagenesis, we have eliminated the role of various structural or thermodynamic properties of these proteins such as the number of amino acid residues, secondary structure content, packing density, electrostriction, dynamics, or thennostability. We have also shown that alpha(N)(T) and E-N,E-sp(T) functions for a given protein are rather insensitive to the small changes in the amino acid sequence, suggesting that alpha(N)(T) and E-N(T) functions might be defined by a topology of a given protein fold. This conclusion is supported by the similarity of alpha(N)(T) and E-N(T) functions for six resurrected ancestral thioredoxins that vary in sequence, but have very similar tertiary structure.