Aggregation of human serum albumin during a thermal viral inactivation step.
A terminal pasteurization step has been used for some plasma-derived protein products such as human serum albumin (HSA), which consists of heating the protein in solution at 60 degrees C for 10 h. Native and denaturing SDS-PAGE and dynamic light scattering were used to follow the stability of HSA during this process. It appears that a thermally unstable fraction, comprised primarily of haptoglobin, is involved in the formation of soluble aggregates of HSA. Therefore, it appears that aggregation during heat treatment is not due to conformational instability of HSA itself, but arises from unfolding of a thermally labile protein impurity. As haptoglobin aggregates, it entraps some HSA, which is present at much higher concentrations. This study emphasizes that, in a complex mixture of naturally occurring proteins, one thermally labile species can trigger aggregation of more stable proteins.
Lin
Jen-Jen
JJ
Center for Pharmaceutical Biotechnology, University of Colorado Denver Health Sciences Center, Denver, CO 80262, USA.
Meyer
Jeffrey D
JD
Carpenter
John F
JF
Manning
Mark Cornell
MC
D006242:Haptoglobins / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008970:Molecular Weight; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors; D038301:Virus Inactivation
D006242:Haptoglobins; D012709:Serum Albumin