1n9j
From Proteopedia
Solution Structure of the 3D domain swapped dimer of Stefin A
Structural highlights
Disease[CYTA_HUMAN] Defects in CSTA are the cause of ichthyosis exfoliative autosomal recessive ichthyosis bullosa of Siemens-like (AREI) [MIM:607936]. A form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.[1] Function[CYTA_HUMAN] This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis.[2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCystatins, an amyloid-forming structural superfamily, form highly stable, domain-swapped dimers at physiological protein concentrations. In chicken cystatin, the active monomer is a kinetic trap en route to dimerization, and any changes in solution conditions or mutations that destabilize the folded state shorten the lifetime of the monomeric form. In such circumstances, amyloidogenesis will start from conditions where a domain-swapped dimer is the most prevalent species. Domain swapping occurs by a rearrangement of loop I, generating the new intermonomer interface between strands 2 and 3. The transition state for dimerization has a high level of hydrophobic group exposure, indicating that gross conformational perturbation is required for domain swapping to occur. Dimerization also occurs when chicken cystatin is in its reduced, molten-globule state, implying that the organization of secondary structure in this state mirrors that in the folded state and that domain swapping is not limited to the folded states of proteins. Although the interface between cystatin-fold units is poorly defined for cystatin A, the dimers are the appropriate size to account for the electron-dense regions in amyloid protofilaments. Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily.,Staniforth RA, Giannini S, Higgins LD, Conroy MJ, Hounslow AM, Jerala R, Craven CJ, Waltho JP EMBO J. 2001 Sep 3;20(17):4774-81. PMID:11532941[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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