Table 1. Summary of the structural analysis of various mutants of human γD crystallin.
S.No. | Mutants | Secondary structure and solvent accessibility of the residue | Non polar residues with increased solvent exposure in the mutant* | Polar residues with increased solvent exposure in the mutant* | Effect on Inter-domain interactions | Intermolecular interactions at the site of mutation |
1 | P24T | Edge strand in the second Greek key (GK) motif in the N-terminal domain is solvent-exposed | Y6,Y16,Y45,Y50,Y62, A63,Y98,F118,W157,A159 | T4,E7,R9,Q12,R14,H15,E17,D21,P23),S30,N33,R36,D38,Y45,Q47,S51,R59,D61,H65Q66,Q67,S72,D73,R76,S87,H88,R89,R95,R99,Q101,C111,Q113,R115,N125,E128,R140,T160,R163 | Indirectly | Not directly affected |
A36P | GK-1motif disturb due to Proline | P43,L53, F118,F173 | R9,N33, C41,Q47, H65,Q66, D 97,R99,C111, | GK1 not involved in interdomain interactions. However, the conformation change and destabilization of GK1 might indirectly affect. | Altered stability and conformation of the GK1 might affect Intermolecular interactions | |
3 | L45PL54P | Residues are in the middle and edge strands, respectively, in GK 2. L45 is buried, L54 is solvent-exposed | L53, M69, L71, | R9, E46, D64, Q66, Q67, S74, R76, R99 | GK2 involved in domain-domain interactions. The conformation and stability of this β sheet is affected due to the presence of prolines | Altered stability and conformation of the GK2 might affect Intermolecular interactions |
4 | R77S | One of the middle strands in GK motif 2 in N-terminal domain is solvent -exposed | Y55, F118, I171 | R9, F24, Q26, N33, E46,Q47,N49,Q66,Q67,S72,S74,S77,D97,R99,Q101 | No | Occurs close to a positively charged patch in symmetry- related molecule |
5 | E107A | Loop connecting the two GKs in C-terminal domain, solvent-exposed | L53,F105,F118 | R9,N33,Q66,R76,H88,R89, D97,R99,Q101,T106,D108,C109,R169 | No | Polar environment in the symmetry- related molecule |
6 | Y134A | Located at the middle strand in GK4, buried | L53, M69, F118, V132, Y139, | R9,N33, E46, D64, N66, N67, S74, R76, D97, R99, Q101,R140, Q143 | Possibly affected as the site occurs in GK4 involved in inter-domain interactions | Does not seem to be affected |
7 | R140X | Three strands corresponding to both the motifs and a loop connecting the two strands | L53,F56,I81,I90,L92,Y98,L112,I121,L124,V126,L127,W131,V132,L133,Y134,L136, | Y45,Q54,R59,R79,S84,H88,E96,D97,Y98,T106,D108,C109,Q113,N119,E120,H122,N125,S130,E135,S137,N138, #Y144,L145,L146,W157,A159,A162,V164,L167,V170 | Affected | Could be affected due to unfolding of the molecule |
8 | W157X | Loop and beta strand at the C-terminal region | F56,I81,L92,L112,I121,L124,W131,V132,L133,Y134,L136,Y139,Y144,L146,Y151,Y154, | Q54,R59,S84,H88,T106,D108,C109,Q113,N119,E120,S130,E135,S137,R142,Y144,Y154, #W157,A159,A162,V164,L167,V170 | Affected | Could be affected due to unfolding of the molecule |
9 | G165fs | L53,F56,I81,L92,F118,W131,V132,L133,Y139, | R9,N33,R59,Q66,Q67,R76,S84,H88,D97,R99,Q101,T106,D108,C109,S130,Y134,#V170 | Affected | Possibly affected due to unfolding |
The residues indicated in italics are the residues buried in the WT but absent in the respective mutants.