1. Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie alpha2 130 Ala --> Pro and Hb Caserta alpha2 26 Ala --> Thr) in a single HBA2 gene
Cristina Passarello, Antonino Giambona, Luciano Prossomariti, Massimiliano Ammirabile, Piero Pucci, Disma Renda, Leonilde Pagano, Aurelio Maggio Br J Haematol. 2008 Oct;143(1):138-42. doi: 10.1111/j.1365-2141.2008.07319.x. Epub 2008 Aug 4.
This study describes a new molecular condition in the alpha(2)-globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G-->A (Hb Caserta) and HBA2 130 G-->C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an alpha-thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with alpha degrees delectional thalassemia.
3. Deciphering the glycosylation code
Christopher R Ellis, William G Noid J Phys Chem B. 2014 Oct 2;118(39):11462-9. doi: 10.1021/jp508535f. Epub 2014 Sep 23.
Asparagine-linked carbohydrates profoundly impact glycoprotein folding, stability, and structure. However, the "glycosylation code" that relates these effects to protein sequence remains unsolved. We report atomically detailed replica exchange molecular dynamics simulations in explicit solvent that systematically investigate the impact of glycosylation upon peptides with the central sequon Pro-Asn-Gly/Ala-Thr-Trp/Ala. These simulations suggest that the effects of glycosylation may be quite sensitive to steric crowding by the side chain immediately following the glycosylation site but less sensitive to stacking interactions with the aromatic Trp residue. In addition, we compare our simulated ensembles with the known structures for full length glycoproteins. These structures corroborate the simulations and also suggest a remarkable consistency between the intraprotein and protein-glycan interactions of natural glycoproteins. Moreover, our analysis highlights the significance of left-handed conformations for compact β-hairpins at glycosylation sites. In summary, these studies elucidate basic biophysical principles for the glycosylation code.