Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage
Proteins exposed to UV radiation are subject to irreversible photodamage through covalent modification of tryptophans (Trps) and other UV-absorbing amino acids. Crystallins, the major protein components of the vertebrate eye lens that maintain lens transparency, are exposed to ambient UV radiation t...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society (ACS)
2012
|
| Online Access: | http://hdl.handle.net/1721.1/73172 https://orcid.org/0000-0001-6174-217X |
| _version_ | 1811078809423708160 |
|---|---|
| author | Callis, Patrik R. King, Jonathan Alan Chen, Jiejin, Ph. D. Massachusetts Institute of Technology |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Callis, Patrik R. King, Jonathan Alan Chen, Jiejin, Ph. D. Massachusetts Institute of Technology |
| author_sort | Callis, Patrik R. |
| collection | MIT |
| description | Proteins exposed to UV radiation are subject to irreversible photodamage through covalent modification of tryptophans (Trps) and other UV-absorbing amino acids. Crystallins, the major protein components of the vertebrate eye lens that maintain lens transparency, are exposed to ambient UV radiation throughout life. The duplicated β-sheet Greek key domains of β- and γ-crystallins in humans and all other vertebrates each have two conserved buried Trps. Experiments and computation showed that the fluorescence of these Trps in human γD-crystallin is very efficiently quenched in the native state by electrostatically enabled electron transfer to a backbone amide [Chen et al. (2006) Biochemistry 45, 11552−11563]. This dispersal of the excited state energy would be expected to minimize protein damage from covalent scission of the excited Trp ring. We report here both experiments and computation showing that the same fast electron transfer mechanism is operating in a different crystallin, human γS-crystallin. Examination of solved structures of other crystallins reveals that the Trp conformation, as well as favorably oriented bound waters, and the proximity of the backbone carbonyl oxygen of the n − 3 residues before the quenched Trps (residue n), are conserved in most crystallins. These results indicate that fast charge transfer quenching is an evolved property of this protein fold, probably protecting it from UV-induced photodamage. This UV resistance may have contributed to the selection of the Greek key fold as the major lens protein in all vertebrates. |
| first_indexed | 2024-09-23T11:05:50Z |
| format | Article |
| id | mit-1721.1/73172 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:05:50Z |
| publishDate | 2012 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/731722022-09-27T17:07:28Z Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage Callis, Patrik R. King, Jonathan Alan Chen, Jiejin, Ph. D. Massachusetts Institute of Technology Massachusetts Institute of Technology. Department of Biology Chen, Jiejin King, Jonathan Alan Proteins exposed to UV radiation are subject to irreversible photodamage through covalent modification of tryptophans (Trps) and other UV-absorbing amino acids. Crystallins, the major protein components of the vertebrate eye lens that maintain lens transparency, are exposed to ambient UV radiation throughout life. The duplicated β-sheet Greek key domains of β- and γ-crystallins in humans and all other vertebrates each have two conserved buried Trps. Experiments and computation showed that the fluorescence of these Trps in human γD-crystallin is very efficiently quenched in the native state by electrostatically enabled electron transfer to a backbone amide [Chen et al. (2006) Biochemistry 45, 11552−11563]. This dispersal of the excited state energy would be expected to minimize protein damage from covalent scission of the excited Trp ring. We report here both experiments and computation showing that the same fast electron transfer mechanism is operating in a different crystallin, human γS-crystallin. Examination of solved structures of other crystallins reveals that the Trp conformation, as well as favorably oriented bound waters, and the proximity of the backbone carbonyl oxygen of the n − 3 residues before the quenched Trps (residue n), are conserved in most crystallins. These results indicate that fast charge transfer quenching is an evolved property of this protein fold, probably protecting it from UV-induced photodamage. This UV resistance may have contributed to the selection of the Greek key fold as the major lens protein in all vertebrates. National Eye Institute (Grant EY 015834) 2012-09-26T13:28:00Z 2012-09-26T13:28:00Z 2009-04 2009-03 Article http://purl.org/eprint/type/JournalArticle 0006-2960 1520-4995 http://hdl.handle.net/1721.1/73172 Chen, Jiejin, Patrik R. Callis, and Jonathan King. “Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage.” Biochemistry 48.17 (2009): 3708–3716. Copyright © 2009 American Chemical Society https://orcid.org/0000-0001-6174-217X en_US http://dx.doi.org/10.1021/bi802177g Biochemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Callis, Patrik R. King, Jonathan Alan Chen, Jiejin, Ph. D. Massachusetts Institute of Technology Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage |
| title | Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage |
| title_full | Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage |
| title_fullStr | Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage |
| title_full_unstemmed | Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage |
| title_short | Mechanism of the Very Efficient Quenching of Tryptophan Fluorescence in Human γD- and γS-Crystallins: The γ-Crystallin Fold May Have Evolved To Protect Tryptophan Residues from Ultraviolet Photodamage |
| title_sort | mechanism of the very efficient quenching of tryptophan fluorescence in human γd and γs crystallins the γ crystallin fold may have evolved to protect tryptophan residues from ultraviolet photodamage |
| url | http://hdl.handle.net/1721.1/73172 https://orcid.org/0000-0001-6174-217X |
| work_keys_str_mv | AT callispatrikr mechanismoftheveryefficientquenchingoftryptophanfluorescenceinhumangdandgscrystallinsthegcrystallinfoldmayhaveevolvedtoprotecttryptophanresiduesfromultravioletphotodamage AT kingjonathanalan mechanismoftheveryefficientquenchingoftryptophanfluorescenceinhumangdandgscrystallinsthegcrystallinfoldmayhaveevolvedtoprotecttryptophanresiduesfromultravioletphotodamage AT chenjiejinphdmassachusettsinstituteoftechnology mechanismoftheveryefficientquenchingoftryptophanfluorescenceinhumangdandgscrystallinsthegcrystallinfoldmayhaveevolvedtoprotecttryptophanresiduesfromultravioletphotodamage |