Sickle Cell Anemia (hemoglobin)

Hemoglobin is the classic example of quaternary protein structure used in many textbooks. Activities include an active-learning paper bioinformatics activity in which students discover reading frames, introns, and the impact of mutations on the function of the β globin gene. Students can also identify promoters and polyadenylation signals. As an extension of the Amino Acid Starter Kit©, students can fold a β globin protein, modeling alpha helices, salt bridges, and coordination of the heme group. A video describes the impact of the sickle cell mutation on hemoglobin structure.

:: Jmol tutorial

This interactive tutorial features quaternary hemoglobin structure, then focuses on β globin to demonstrate N and C termini, heme group, secondary structural features, coordination of heme group with histidines 63 and 92, location of hydrophobic and hydrophilic sidechains, and formation of salt bridges.

:: Sickle Cell Animation

This animation describes the impact of the sickle cell mutation leading to Sickle Cell Disease.

:: Clickable blood

This illustration by David Goodsell depicting components of the blood allows you to scroll over various proteins and see their structure and background information in windows on the right of the screen.

:: Molecule of the Month extension

:: β Globin Paper Bioinformatics

This hands-on activity features forward reading frames, promoters, intron splice sequences, polyadenylation sequences, and mutations leading to sickle cell anemia and various β0- and β+-thalessemias. Students work backwards from protein sequence to annotate the features of the gene.

Available for loan from MSOE Model Lending Library
Available for purchase from 3D Molecular Designs

:: Hemoglobin References

Bunn, H. Franklin. 1981. Evolution of Mammalian Hemoglobin Function. Blood 58(2): 189-197.

Collins, Francis S., Metherall, James E., Yamkawa, Minoru, Pan, Julian, Weissman, Sherman M and Forget, Bernard G. 1985. A point mutation in the Aγ-globin gene promoter in Greek hereditary persistence of fetal haemoglobin [requires account or payment]. Nature: 313:325-326.

Efremov, D.G., Dimovski, A.J. and Huisman, T.H.J. 1994. The -158 (C→ T) Promoter Mutation Is Responsible for the Increased Transcription of the 3’ γ Gene in the Atlanta Type of Hereditary Persistence of Fetal Hemoglobin. Blood 83(11):3350-3355.

Forget, B.G. 1998. Molecular basis of hereditary persistence of fetal hemoglobin. Ann. NY Acad. Sci. 850(June 30):38-44.

Gelinas R, Yagi M, Endlich B, Lotshaw C, Kazazian HH Jr, Stamatoyannopoulos G. 1985. Sequences of G gamma, A gamma, and beta genes of the Greek (A gamma) HPFH mutant: evidence for a distal CCAAT box mutation in the A gamma gene. Prog. Clin. Biol. Res 191: 125-139.

Gumucio, Deborah L., Rood, Kirsten L., Gray, Todd A., Riordan, Maureen F., Sartor, Carolyn I. and Collins, Francis S. 1988. Nuclear Proteins That Bind the Human γ-Globin Gene Promoter: Alterations in Binding Produced by Point Mutations Associated with Hereditary Persistence of Fetal Hemoglobin. Molec. Cell. Biol. 8(12):5310-5322.

Peri, Krishna G., Gagnon, Carmen and Bard, Henry. 1998. Quantitative Correlation between Globin mRNAs and Synthesis of Fetal and Adult Hemoglobins during Hemoglobin Switchover in the Perinatal Period. Pediatric Res. 43(4): 509-513.