Lens Crystallins and Their Microbial Homologs: Structure, Stability, and Function

作者：Rainer Jaenicke, C. Slingsby · 发表于：Critical Reviews in Biochemistry and Molecular Biology · 年份：2001 · DOI：10.1080/20014091074237 · 被引用次数：155 · 研究领域：Protein Structure and Dynamics、Enzyme Structure and Function、Connexins and lens biology

abg-Crystallins are the major protein components in the vertebrate eye lens--a as a molecular chaperone and b and g as structural proteins. Surprisingly, the latter two share some structural characteristics with a number of microbial stress proteins. The common denominator is not only the Greek key topology of their polypeptide chains but also their high intrinsic stability, which, in certain microbial crystallin homologs, is further enhanced by high-affinity Ca2+-binding. Recent studies of natural and mutant vertebrate bg-crystallins as well as spherulin 3a from Physarum polycephalum and Protein S from Myxococcus xanthus allowed the correlation of structure and stability of crystallins to be elucidated in some detail. From the thermodynamic point of view, stability increments come from (1) local interactions involved in the close packing of the cooperative units, (2) the all-b secondary structure of the Greek-key motif, (3) intramolecular interactions between domains, (4) intermolecular domain interactions, including 3D domain swapping and (v) excluded volume effects due to "molecular crowding" at the high cellular protein concentrations. Apart from these contributions to the Gibbs free energy of stability, significant kinetic stabilization originates from the high activation energy barrier determining the rate of unfolding from the native to the unfolded state. From the functional point of view, the high stability is responsible for the long-term transparency of the eye len...