PDBsum entry 2kdl

Human serum albumin binding protein

PDB id: 2kdl

Contents

Protein chain

56 a.a. *

* Residue conservation analysis

PDB id:

2kdl

Name:

Human serum albumin binding protein

Title:

Nmr structures of ga95 and gb95, two designed proteins with 95% sequence identity but different folds and functions

Structure:

Designed protein. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: designed protein

NMR struc:

20 models

Authors:

Y.He,P.Alexander,Y.Chen,P.Bryan,J.Orban

Key ref:

P.A.Alexander et al. (2009). A minimal sequence code for switching protein structure and function. Proc Natl Acad Sci U S A, 106, 21149-21154. PubMed id: 19923431 DOI: 10.1073/pnas.0906408106

Date:

12-Jan-09 Release date: 29-Dec-09

Protein chain

No UniProt id for this chain

Struc: 56 a.a.

DOI no: 10.1073/pnas.0906408106

Proc Natl Acad Sci U S A 106:21149-21154 (2009)

PubMed id: 19923431

A minimal sequence code for switching protein structure and function.

P.A.Alexander, Y.He, Y.Chen, J.Orban, P.N.Bryan.

ABSTRACT

We present here a structural and mechanistic description of how a protein changes its fold and function, mutation by mutation. Our approach was to create 2 proteins that (i) are stably folded into 2 different folds, (ii) have 2 different functions, and (iii) are very similar in sequence. In this simplified sequence space we explore the mutational path from one fold to another. We show that an IgG-binding, 4beta+alpha fold can be transformed into an albumin-binding, 3-alpha fold via a mutational pathway in which neither function nor native structure is completely lost. The stabilities of all mutants along the pathway are evaluated, key high-resolution structures are determined by NMR, and an explanation of the switching mechanism is provided. We show that the conformational switch from 4beta+alpha to 3-alpha structure can occur via a single amino acid substitution. On one side of the switch point, the 4beta+alpha fold is >90% populated (pH 7.2, 20 degrees C). A single mutation switches the conformation to the 3-alpha fold, which is >90% populated (pH 7.2, 20 degrees C). We further show that a bifunctional protein exists at the switch point with affinity for both IgG and albumin.

Selected figure(s)

Figure 4.
Cartoon depiction of backbone topology of G[A]95 and G[B]95. Residues 1–8 are blue, 9–23 are green, 24–37 are red, 38–52 are yellow, and 53–56 are cyan.

Figure 6.
Switching mechanism. Alternative conformations of the N-terminal (orange) and C-terminal (blue) amino acids in the 3-α and 4β+α folds. The critical switch amino acid occurs at position 45 (red). Also depicted are the hydrophobic packing of the N- and C-terminal amino acids in the core of the 4β+α fold.

Figures were selected by the author.