Essential role of proline isomerization in stefin B tetramer formation.
Here we present the tetrameric structure of stefin B, which is the result of a process by which two domain-swapped dimers of stefin B are transformed into tetramers. The transformation involves a previously unidentified process of extensive intermolecular contacts, termed hand shaking, which occurs concurrently with trans to cis isomerization of proline 74. This proline residue is widely conserved throughout the cystatin superfamily, a member of which, human cystatin C, is the key protein in cerebral amyloid angiopathy. These results are consistent with the hypothesis that isomerization of proline residues can play a decisive role in amyloidogenesis.
Jenko Kokalj
Sasa
S
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
Guncar
Gregor
G
Stern
Igor
I
Morgan
Gareth
G
Rabzelj
Sabina
S
Kenig
Manca
M
Staniforth
Rosemary A
RA
Waltho
Jonathan P
JP
Zerovnik
Eva
E
Turk
Dusan
D
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002942:Circular Dichroism; D003432:Cross-Linking Reagents; D018360:Crystallography, X-Ray; D055313:Cystatin B; D015891:Cystatins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D014644:Genetic Variation; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D008027:Light; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011392:Proline / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D014270:Trifluoroethanol / Q000494:pharmacology
D000682:Amyloid; C524994:CSTB protein, human; D003432:Cross-Linking Reagents; D015891:Cystatins; D012996:Solutions; D012694:Serine; D014270:Trifluoroethanol; D055313:Cystatin B; D011392:Proline; D005976:Glutaral