Sequence determinants of thermodynamic stability in a WW domain--an all-beta-sheet protein.


Abstract

The stabilities of 66 sequence variants of the human Pin1 WW domain have been determined by equilibrium thermal denaturation experiments. All 34 residues composing the hPin1 WW three-stranded beta-sheet structure could be replaced one at a time with at least one different natural or non-natural amino acid residue without leading to an unfolded protein. Alanine substitutions at only four positions within the hPin1 WW domain lead to a partially or completely unfolded protein-in the absence of a physiological ligand. The side chains of these four residues form a conserved, partially solvent-inaccessible, continuous hydrophobic minicore comprising the N- and C-termini. Ala mutations at five other residues, three of which constitute the ligand binding patch on the concave side of the beta-sheet, significantly destabilize the hPin1 WW domain without leading to an unfolded protein. The remaining mutations affect protein stability only slightly, suggesting that only a small subset of side chain interactions within the hPin1 WW domain are mandatory for acquiring and maintaining a stable, cooperatively folded beta-sheet structure. Study holds ProTherm entries: 25101, 25102, 25103, 25104, 25105, 25106, 25107, 25108, 25109, 25110, 25111, 25112, 25113, 25114, 25115, 25116, 25117, 25118, 25119, 25120, 25121, 25122, 25123, 25124, 25125, 25126, 25127, 25128, 25129, 25130, 25131, 25132, 25133, 25134, 25135, 25136, 25137, 25138, 25139, 25140, 25141, 25142, 25143, 25144, 25145, 25146, 25147, 25148, 25149, 25150, 25151, 25152, 25153, 25154, 25155, 25156, 25157, 25158, 25159, 25160, 25161, 25162, 25163, 25164, 25165, 25166, 25167, 25168, 25169, 25170, 25171, 25172, 25173, 25174, 25175, 25176, 25177, 25178, 25179, 25180, 25181, 25182, 25183, 25184, 25185, 25186, 25187, 25188, 25189, 25190, 25191, 25192, 25193, 25194, 25195, 25196, 25197, 25198, 25199, 25200, 25201, 25202, 25203, 25204, 25205, 25206, 25207, 25208, 25209, 25210, 25211, 25212, 25213, 25214 Extra Details: WW domain; Ala scanning; Gly scanning; side chain mutagenesis; protein stability; protein folding; beta-sheet

Submission Details

ID: xT7jFTKE4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:55 p.m.

Version: 1

Publication Details
J├Ąger M;Dendle M;Kelly JW,Protein Sci. (2009) Sequence determinants of thermodynamic stability in a WW domain--an all-beta-sheet protein. PMID:19565466
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 UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Q13526 PIN1_HUMAN
99.4 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Q4R383 PIN1_MACFA
98.2 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Q5BIN5 PIN1_BOVIN
95.2 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Q9QUR7 PIN1_MOUSE
90.5 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 O15428 PINL_HUMAN