Structural and functional properties of lengsin, a pseudo-glutamine synthetase in the transparent human lens.
Lengsin (LGS) is an abundant transcript in the human lens, encoding a predicted polypeptide similar to glutamine synthetase (GS). We show that a major alternatively spliced product of LGS codes for a 57kDa polypeptide that assembles into a catalytically inactive dodecamer, cross-reacts with anti-GS antibodies, and is expressed at high levels in transparent, but not cataractous, human lenses. Based on this characteristic oligomeric organization, preferential expression in the transparent lens, and amyloid-beta association previously reported for GS, a potential chaperone-like role of LGS has been investigated. We find that LGS has six binding sites for the hydrophobic surface probe bis-ANS and relieves cellular toxicity caused by amyloid-beta expression in a folding-impaired yeast mutant. While documenting the structural similarity between LGS and prokaryotic GS-I, the data rule out any involvement of lengsin in glutamine biosynthesis and suggest an unrelated role that may be important for lens homeostasis and transparency.
Grassi
Francesca
F
Dipartimento di Biochimica e Biologia Molecolare, Università di Parma, Viale G.P. Usberti 23/A, I-43100 Parma, Italy.
Moretto
Nadia
N
Rivetti
Claudio
C
Cellai
Sara
S
Betti
Marco
M
Márquez
Antonio J
AJ
Maraini
Giovanni
G
Ottonello
Simone
S
D017398:Alternative Splicing; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D002386:Cataract / Q000378:metabolism; D003429:Cross Reactions; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005456:Fluorescent Dyes; D005974:Glutamate-Ammonia Ligase / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010802:Phylogeny
D016229:Amyloid beta-Peptides; D000817:Anilino Naphthalenesulfonates; D005136:Eye Proteins; D005456:Fluorescent Dyes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C035763:5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate); D005974:Glutamate-Ammonia Ligase; C507977:LGSN protein, human