Micellar subunit assembly in a three-layer model of oligomeric alpha-crystallin.


Abstract

Differential scanning calorimetry was performed to monitor the heat-induced changes that occur in the structural domain of lens alpha-crystallin. Circular dichroism and fluorescence also were used to resolve the controversial issue of the quaternary structure of alpha-crystallin. Based on the thermal behavior as monitored by these techniques, a model is proposed that can account for all previous data as well as the currently reported thermal data. The proposed model of native alpha-crystallin has a three-layer structure in which the inner layer (core) is a micelle containing 12 subunits arranged in cuboctahedral symmetry. The apolar region is directed inward constituting a hydrophobic core similar to a micelle and adding structural stability. A second layer of six subunits has a similar but not identical structure to the first layer, directing its apolar face toward the hydrophobic core. Thus, these two layers constitute a micelle-like structure with octahedral symmetry. The third layer adds more subunits for a total of not more than 24. Differential scanning calorimetry, circular dichroism, and fluorescence studies indicated that the inner two-layer structure of molecular mass 360 kDa is highly stable and is most likely of the alpha m form. The three-layer structure of the native protein, however, is rather unstable. At 35-45 degrees C the outer layer dissociates from the inner two layers, and at higher temperatures rapidly reassociates to a slightly modified two-layer structure with a stability similar to that of alpha m. The proposed model does not require any specific assembly of the alpha A and alpha B subunits in each layer, but the fluorescence results suggest that the native inner two layers probably contain mostly alpha A. Study holds ProTherm entries: 5161 Extra Details: structural domain; quaternary structure; hydrophobic core;,structural stability

Submission Details

ID: M3UVLnS

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:28 p.m.

Version: 1

Publication Details
Walsh MT;Sen AC;Chakrabarti B,J. Biol. Chem. (1991) Micellar subunit assembly in a three-layer model of oligomeric alpha-crystallin. PMID:1939070
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
3L1E 2010-05-12 1.15 Bovine AlphaA crystallin Zinc Bound
3L1F 2010-05-12 1.53 Bovine AlphaA crystallin

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
90.8 Alpha-crystallin A chain P02487 CRYAA_BRAVA
90.2 Alpha-crystallin A chain P02502 CRYAA_MACRU
91.9 Alpha-crystallin A chain P02486 CRYAA_CHOHO
90.8 Alpha-crystallin A chain P02501 CRYAA_ORYAF
92.5 Alpha-crystallin A chain P82533 CRYAA_ERIEU
92.5 Alpha-crystallin A chain P02499 CRYAA_PROCA
94.8 Alpha-crystallin A chain P02488 CRYAA_MACMU
94.2 Alpha-crystallin A chain P02498 CRYAA_LOXAF
94.2 Alpha-crystallin A chain P02489 CRYAA_HUMAN
94.2 Alpha-crystallin A chain A0A140G945 CRYA2_HUMAN
95.4 Alpha-crystallin A chain P02484 CRYAA_MANJA
96.0 Alpha-crystallin A chain P68406 CRYAA_TUPGL
96.0 Alpha-crystallin A chain P68405 CRYAA_MERUN
95.4 Alpha-crystallin A chain P68286 CRYAA_PERPO
95.4 Alpha-crystallin A chain P68287 CRYAA_OTOCR
96.0 Alpha-crystallin A chain P02492 CRYAA_OCHPR
96.0 Alpha-crystallin A chain P02483 CRYAA_NEOVI
96.5 Alpha-crystallin A chain P68288 CRYAA_ZALCA
96.5 Alpha-crystallin A chain P68289 CRYAA_HALGR
96.0 Alpha-crystallin A chain P02494 CRYAA_EULFU
97.1 Alpha-crystallin A chain P02482 CRYAA_ARTJA
96.5 Alpha-crystallin A chain P68283 CRYAA_PEDCA
96.5 Alpha-crystallin A chain P68281 CRYAA_CAVPO
97.1 Alpha-crystallin A chain P02477 CRYAA_PHOPH
97.1 Alpha-crystallin A chain P02480 CRYAA_MELUS
97.1 Alpha-crystallin A chain P02478 CRYAA_HORSE
97.1 Alpha-crystallin A chain P02493 CRYAA_RABIT
98.3 Alpha-crystallin A chain P68282 CRYAA_FELCA
98.3 Alpha-crystallin A chain P68280 CRYAA_CANLF
98.8 Alpha-crystallin A chain P02472 CRYAA_CAMDR
97.7 Alpha-crystallin A chain P02479 CRYAA_CERSI
97.7 Alpha-crystallin A chain P02475 CRYAA_PIG
98.3 Alpha-crystallin A chain P02474 CRYAA_BALAC
98.3 Alpha-crystallin A chain P02476 CRYAA_TAPIN
98.8 Alpha-crystallin A chain P82531 CRYAA_PTEPO
99.4 Alpha-crystallin A chain P68285 CRYAA_HIPAM
99.4 Alpha-crystallin A chain P68284 CRYAA_GIRCA
99.4 Alpha-crystallin A chain Q5ENZ0 CRYAA_SHEEP
100.0 Alpha-crystallin A chain P02470 CRYAA_BOVIN