mutations' effect on secondary structure

Question

[lait]

What I used t know is that when mutation takes place in a protein sequence and some amino acids are substituted with other amino acids having different chemical properties, then this will certainly alter the secondary structure of the protein sequence.

Recently I saw a case were 4 amino acids in a protein sequence are substituted with amino acids having same chemical properties (for example, E substituted with D), and this did affect the secondary structure of the sequence (beta sheets start/end positions changed).

1. What is the explanation for this ?
2. would this affect the function of the protein sequence also ?

[Joe]

Is this really within Biostars remit? Not exactly a bioinfx query

Answer 1

[apa@stowers]

This kind of sounds like an exam question, but, it is 9 months old...

Just about anything can impact the protein function, in theory. Depending on the situation, you can even get a disease phenotype from an L->I mutation, one of the most innocuous and common substitutions. Without knowing your exact case, it's hard to say why.

The basic chemical properties like polarity, pH, aromaticity aren't everything -- you also have pKas and isoelectric points, steric effects, helical propensities, cation affinities, types of bonds the side chain can engage in, etc, etc. Different amino acids are different!

One structural context may be very lax with amino acid properties (free loop), while others are very fine-tuned (inter-subunit bridge). You just don't know until you know (read: have the crystal structure).

Also, you can impact function without affecting secondary or tertiary structure. A mutation can affect the ability to interact with other proteins, receive PTMs, bind ligands, etc.