This is a not trivial question. A complete answer would be complex, but the answer has to do with the interface of structure and function. Proteins tend to fold into domains, which have more interactions within them than with other regions, and may vary from roughly ~100 to 300 residues. These domains can have individual functions. Insertions and deletions between domains may therefore occur in regions that are flexible linkers or regulator regions that will tend to be more organism dependent than the functional domains that are more evolutionarily restrained by their functions and their need to retain a stable domain fold. Within domains, however, insertions and deletions can still occur in flexible loops or other protrusions without impact fold or function. At the motif level, we see greater conservation of sequence regions that may have to do with ATP binding or hydrolysis (The Walker A and Walker B regions) or with conserved protein interactions (the PCNA interacting PIP box), as examples. These conserved sequences may lie within functional domains such as helicases, polymerases, and kinases that maintain similar folds for their family members but allow insertions and deletions within protruding loop regions and even more so between domains such as seen for the DNA helicase-nuclease DNA2. The sequences are still similar as the functional and structural domains are largely conserved despite changes between them. The insertions and deletions effectively cluster to regions with less impact on fold and function making the sequences functionally and structurally similar despite insertions and deletions as these do not largely impact on the important similarities.
Dear Marakaz Good day to you and Greeting
• homology: similarity due to descent from a common
ancestor
• often we can infer homology from similarity
• thus we can sometimes infer structure/function from
sequence similarity
- some insertions and deletions may not significantly
affect the structure of a protein
• the sequences we’re comparing probably differ in length
• there may be only a relatively small region in the
sequences that match
• we want to allow partial matches (i.e. some amino acid
pairs are more substitutable than others)
• variable length regions may have been inserted/deleted
from the common ancestral sequence
Hello Marakaz you read this paper is very useful http://www.genetics.org/content/169/3/1521.full.pdf+html
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