PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Related Articles
Drug Discovery: Solving the Structure of an Anti-hypertension Drug Target
July 2015
Retrospective: 7,000 Structures Closer to Understanding Biology
July 2015
Design and Evolution: Bespoke Design of Repeat Proteins
June 2015
Design and Evolution: Molecular Sleuthing Reveals Drug Selectivity
June 2015
Design and Evolution: Tunable Antibody Binders
June 2015
Design and Evolution: Unveiling Translocator Proteins
June 2015
Evolution of Photoconversion
June 2015
Families in Gene Neighborhoods
June 2015
Protein Folding and Misfolding: A TRiC-ster that Follows the Rules
March 2015
Protein Folding and Misfolding: Beneficial Aggregation
March 2015
Peptidyl-carrier Proteins
October 2014
Predicting Protein Crystal Candidates
October 2014
Protein and Peptide Synthesis: Coming Full Circle
October 2014
Protein and Peptide Synthesis: Sensing Energy Balance
October 2014
Mining Protein Dynamics
May 2014
Novel Proteins and Networks: Assigning Function
May 2014
Novel Proteins and Networks: Polysaccharide Metabolism in the Human Gut
May 2014
Design and Discovery: Evolutionary Dynamics
January 2014
Design and Discovery: Identifying New Enzymes and Metabolic Pathways
January 2014
Design and Discovery: Virtual Drug Screening
January 2014
Caught in the Act
December 2013
Microbiome: Insights into Secondary Bile Acid Synthesis
September 2013
Microbiome: Structures from Lactic Acid Bacteria
September 2013
The Immune System: A Brotherhood of Immunoglobulins
June 2013
The Immune System: Super Cytokines
June 2013
Design and Discovery: A Cocktail for Proteins Without ID
February 2013
Design and Discovery: Enzyme Reprogramming
February 2013
Design and Discovery: Extreme Red Shift
February 2013
Design and Discovery: Flexible Backbone Protein Redesign
February 2013
Designer Proteins
February 2013
Membrane Proteome: Sphingolipid Synthesis Selectivity
December 2012
Symmetry from Asymmetry
October 2012
Serum albumin diversity
August 2012
Pocket changes
July 2012
Predictive protein origami
July 2012
Targeting Enzyme Function with Structural Genomics
July 2012
Finding function for enolases
June 2012
Substrate specificity sleuths
April 2012
Disordered Proteins
February 2012
Metal mates
February 2012
Making invisible proteins visible
October 2011
Alpha/Beta Barrels
October 2010
Deducing function from small structural clues
February 2010
Extremely salty
February 2010
Membrane proteins spotted in their native habitat
January 2010
How does Dali work?
December 2009
Secretagogin
December 2009
Designing activity
September 2008

Research Themes Protein design

Serum albumin diversity

SBKB [doi:10.1038/sbkb.2011.91]
Featured Article - August 2012
Short description: Serum albumin is an abundant plasma protein that can cause allergic reactions. The crystal structures of bovine, horse and rabbit serum albumin now provide insight into these properties.

Molecular surfaces of BSA, ESA and RSA with residues that are not conserved with HSA colored according to number of SAs from same or similar order in which the residue is conserved (see color scale above). Figure courtesy of Maks Chruszcz.

Serum albumin (SA) is the most abundant protein in mammalian plasma, reaching a concentration of ca. 0.6mM. SA maintains the osmotic pressure in plasma and also serves as a carrier for myriad ligands, including metabolites, nutrients, fatty acids and ions such as Ca2+ and Mg2+. SAs of animal origin share ca. 60% identity with human SA (HSA). Despite this high degree of similarity, animal SAs can be allergenic, with IgE antibodies showing cross-reactivity to different species' SAs — a feature with considerable clinical implications. For example, a person with an allergy to bovine SA (present in cow's milk and meat) could have an allergic reaction to dog or cat dander (which also contains SA) without ever being exposed to the latter antigens.

Several structures of HSA have been published, but not those of other animals. In order to understand the differences between HSA and other mammalian orthologs, and the basis for allergic responses to the latter, Minor, Chruszcz and colleagues (PSI NYSGRC) solved bovine (BSA), equine (ESA) and rabbit (RSA) SA crystal structures. BSA is a major allergen in bovine meat, whereas ESA and RSA can cause allergic reactions by inhalation. This work allows the comparison of these animal SAs to HSA and provides a structural context within which to understand their antigenic properties.

The structures of animal SAs are overall quite similar to HSA, with an average root-mean-square deviation of 1.1–1.2 Å. The heart-shaped protein is formed by three domains (I, II, III), each divided into two subdomains (A and B). Of note, the BSA structure showed three ordered Ca2+ ions bound within domain I — though Ca2+ binding to SA had been previously studied, the exact location of the binding sites was unknown. The ESA and RSA structures contained a number of unidentified ligands, including one bound to a site that had not been previously observed in HSA.

Finally, by mapping the regions or residues known to be involved in antigenicity of the different SAs onto the structures, the authors could define potential epitopes and understand the basis for cross-reactivity by considering the surface exposure of those residues and their conservation among SAs. For BSA, previously well characterized in immunological studies, such analysis highlighted two main regions with considerable differences to HSA, both on subdomain IB; other regions (in the loop connecting IIA and IIB, and in IIIA and IIB) can also contribute to the antigenicity of BSA.

Inês Chen

References

  1. K.A. Majorek et al. Structural and immunologic characterization of bovine, horse, and rabbit serum albumins.
    Mol Immunol. 52, 174-182 (2012). doi:10.1016/j.molimm.2012.05.011

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health